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Background Tolvaptan (TLV) is effective for acute heart failure (HF) with congestion, but its long-term administration in patients with chronic HF (CHF) remains controversial. Moreover, the cost-effectiveness of TLV for CHF treatment has not yet been investigated. Thus, we sought to validate the cost-effectiveness of TLV for CHF treatment in Japan. Methods A Markov model was developed to compare total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) between long-term TLV strategy and the standard strategy using furosemide for CHF. The target population included 75-year-old patients with CHF. The effectiveness of the TLV strategy for CHF treatment was determined based on a systematic review and meta-analysis. We used a 10-year horizon, with sensitivity analyses for significant variables and a scenario analysis for patients with CHF receiving high-dose furosemide (≥60 mg per day). Results In the base case analysis, the total cost of the long-term TLV strategy was higher than that of the standard strategy (\3,243,779 vs. \1,179,964). The total QALYs of the long-term TLV strategy were lower than those of the standard strategy (4.52 vs 4.59). Thus, a standard TLV prescription for CHF treatment has no clinical or economic benefit. In the scenario analysis (i.e. in patients with CHF receiving high-dose furosemide), the long-term TLV strategy was more effective (total QALYs, 5.10 vs. 4.41) but more expensive (total costs, \3,540,558 vs. \1,272,208) than the standard strategy. The ICER of the TLV strategy against the standard strategy (¥3,289,579/QALY) was below the willingness-to-pay of \5,000,000, which suggests that the long-term TLV strategy is cost-effective relative to the standard strategy in patients with CHF receiving high-dose furosemide. Conclusions Long-term TLV administration did not provide a clear benefit for all patients with CHF. However, this treatment strategy may be a cost-effective therapeutic option for patients who require high-dose furosemide.

To determine the value of early exome sequencing (eES) relative to the current typical care (TC) in the diagnosis of newborns with suspected severe mitochondrial disorders (MitD). We used a decision tree–Markov hybrid to model neonatal intensive care unit (NICU)–related outcomes and costs, lifetime costs and quality-adjusted life-years among patients with MitD. Probabilities, costs, and utilities were populated using published literature, expert opinion, and the Pediatric Health Information System database. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were calculated from lifetime costs and quality-adjusted life-years for singleton and trio eES, and TC. Robustness was assessed using univariate and probabilistic sensitivity analyses (PSA). Scenario analyses were also conducted. Findings indicate trio eES is a cost-minimizing and cost-effective alternative to current TC. Diagnostic probabilities and NICU length-of-stay were the most sensitive model parameters. Base case analysis demonstrates trio eES has the highest incremental NMB, and PSA demonstrates trio eES had the highest likelihood of being cost-effective at a willingness-to-pay (WTP) of $200,000 relative to TC, singleton eES, and no ES. Trio and singleton eES are cost-effective and cost-minimizing alternatives to current TC in diagnosing newborns suspected of having a severe MitD.

Background Currently it remains difficult to identify patients most likely to benefit from radiotherapy (RT) for ductal carcinoma-in-situ (DCIS), thus leading to wide variation in practice patterns. The genomic risk assessment tool DCISionRT (PreludeDX) has been validated to prognosticate recurrence risk and predict RT benefit. We aimed to study the cost-effectiveness analysis comparing DCIS treatments based on DCISionRT testing to traditional clinicopathologic risk factors. Patients and Methods A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing breast-conserving surgery with or without RT using DCISionRT testing vs. traditional clinicopathologic risk factors. Clinical parameters were obtained from clinical trial data and cross-validation studies. Cost data were based on 2019 Medicare reimbursement. Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained comparing DCIS treatments using DCISionRT testing to traditional clinicopathologic risk factors and evaluated with a willingness-to-pay threshold of US$100,000 per QALY gained. To account for uncertainty, 1-way and probabilistic sensitivity analyses were performed. Results Base case analysis showed that DCIS management using DCISionRT testing was a cost-effective strategy, resulting in an ICER of $74,331 per QALY gained compared to clinicopathology-based treatment. Model results were sensitive to a variation of the proportion of genomic-high, low-risk patients receiving RT in DCISionRT testing strategy, and changes in DCISionRT testing cost. Conclusion DCISionRT testing could potentially be a cost-effective strategy compared to traditional decision making for DCIS treatments, optimizing RT benefit based on an accurate recurrence risk assessment.

To examine the cost-effectiveness of prophylactic probiotics on necrotizing enterocolitis (NEC) prevention in very low birth weight (VLBW) infants. We built a decision-analytic model using TreeAge. Effectiveness was assessed using quality-adjusted life-years (QALY). Primary outcome was an incremental cost-effectiveness ratio (ICER) expressed as cost per QALY gained. Costs were expressed in 2017 US dollars. Deterministic and probabilistic sensitivity analyses (SA) were performed. For the base case analysis, the ICER of probiotics versus no probiotics for the prevention of NEC in VLBW infants was $1868/QALY. SA revealed that probiotics became cost-saving at a NEC rate of 6.5% and higher or with incremental NEC cost of $37,500 or higher. Our model demonstrated that prophylactic probiotics were a cost-effective strategy in NEC reduction. SA confirmed that the model is customizable to various clinical settings and thus, can aid in understanding the economic impact of this intervention.

To evaluate the cost-effectiveness of DECT versus multiphasic CT and MRI for characterizing small incidentally detected indeterminate renal lesions using a Markov Monte Carlo decision-analytic model. Incidental renal lesions are commonly encountered due to the increasing utilization of medical imaging and the increasing prevalence of renal lesions with age. Currently recommended imaging modalities to further characterize incidental indeterminate renal lesions have some inherent drawbacks. Single-phase DECT may overcome these limitations, but its cost-effectiveness remains uncertain. A decision-analytic (Markov) model was constructed to estimate life expectancy and lifetime costs for otherwise healthy 64-year-old patients with small (≤ 4 cm) incidentally detected, indeterminate renal lesions on routine imaging (e.g., ultrasound or single-phase CT). Three strategies for evaluating renal lesions for enhancement were compared: multiphase SECT (e.g., true unenhanced and nephrographic phase), multiphasic MRI, and single-phase DECT (nephrographic phase in dual-energy mode). The model incorporated modality-specific diagnostic test performance, incidence, and prevalence of incidental renal cell carcinomas (RCCs), effectiveness, costs, and health outcomes. An incremental cost-effectiveness analysis was performed to identify strategy preference at willingness-to-pay (WTP) thresholds of $50,000 and $100,000 per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analysis were performed. In the base case analysis, expected mean costs per patient undergoing characterization of incidental renal lesions were $2567 for single-phase DECT, $3290 for multiphasic CT, and $3751 for multiphasic MRI. Associated quality-adjusted life-years were the highest for single-phase DECT at 0.962, for multiphasic MRI it was 0.940, and was the lowest for multiphasic CT at 0.925. Because of lower associated costs and higher effectiveness, the single-phase DECT strategy dominated the other two strategies. Single-phase DECT is potentially more cost-effective than multiphasic SECT and MRI for evaluating small incidentally detected indeterminate renal lesions.

ImportanceTransoral robotic surgery (TORS) and transoral laser micro-surgery (TLM) are two different but competing minimally invasive techniques to surgically remove operable oropharyngeal squamous cell cancers (OPSCC). As of now, no comparative analysis as to the cost-utility of these techniques exists.ObjectiveRecent population-level data suggest for TORS and TLM equivalent tumor control, but different total costs, need for adjuvant chemoradiation, and learning curves. Therefore, the objective of this study was to compare TORS and TLM from the cost-utility (C/U) point of view using a decision-analytical model from a Swiss hospital perspective.DesignOur decision-analytical model combines decision trees and a Markov model to compare TORS and TLM strategies. Model parameters were quantified using available literature, original cost data from two Swiss university tertiary referral centers, and utilities elicited directly from a Swiss population sample using standard gamble. C/U and sensitivity analyses were used to generate results and gauge model robustness.SettingSwiss hospital perspectiveInterventionCost-utility analysisMain outcome measureComparative cost-utility data from TLM and TORSResultsIn the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS would reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment (pTorsAlone>0.407), whereby in an interval between 55%-62% (pTorsAlone 0.38-0.45) cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Also, exceeding 29% of TLM patients requiring a re-operation for inadequate margins renders TORS more cost-effective.ConclusionTLM is more cost-effective than TORS. However, this advantage is sensitive to various parameters i.e. the number of re-operations and adjuvant treatment.Key pointsQuestionCompare cost-utility of TORS versus TLMFindingsIn the base case analysis TLM dominates TORS, even if the costs for TORS would reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55%-62% cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Exceeding 29% of TLM patients requiring a re-operation for inadequate margins renders TORS more cost-effective.MeaningTLM is more cost-effective than TORS. However, this advantage is sensitive to the number of re-operations and adjuvant treatment

Purpose To compare the cost-effectiveness of nonoperative management, particulated juvenile allograft cartilage (PJAC), and matrix-induced autologous chondrocyte implantation (MACI) in the management of patellar chondral lesions. Methods A Markov model was utilized to evaluate cost-effectiveness of three strategies for symptomatic patellar chondral lesions: (1) nonoperative management, (2) PJAC, and (3) MACI. Model inputs (transition probabilities, utilities, and costs) were derived from literature review and an institutional cohort of 67 patients treated with PJAC for patellar chondral defects (mean age 26 years, mean lesion size 2.7 cmˆ2). Societal and payer perspectives over a 15-year time horizon were evaluated. The principal outcome measure was the incremental cost-effectiveness ratio (ICER) using a $100,000/quality-adjusted life year (QALY) willingness-to-pay threshold. Sensitivity analyses were performed to assess the robustness of the model and the relative effects of variable estimates on base case conclusions. Results From a societal perspective, nonoperative management, PJAC, and MACI cost $4,140, $52,683, and $83,073 and were associated with 5.28, 7.22, and 6.92 QALYs gained, respectively. PJAC and MACI were cost-effective relative to nonoperative management (ICERs $25,010/QALY and $48,344/QALY, respectively). PJAC dominated MACI in the base case analysis by being cheaper and more effective, but this was sensitive to the estimated effectiveness of both strategies. PJAC remained cost-effective if PJAC and MACI were considered equally effective. Conclusions In the management of symptomatic patellar cartilage defects, PJAC and MACI were both cost-effective compared to nonoperative management. Due to the need for one surgery instead of two, and less costly graft material, PJAC was cheaper than MACI. Consequently, when PJAC and MACI were considered equally effective, PJAC was more cost-effective than MACI. Sensitivity analyses accounting for the lack of robust long-term data for PJAC or MACI demonstrated that the cost-effectiveness of PJAC versus MACI depended heavily on the relative probabilities of yielding similar clinical results.

There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients.Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening.In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality.Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.

Clinical and patient-reported outcomes were reported for carious primary molars treated with the Hall technique (HT) as compared with conventional carious tissue removal and restorations (i.e., conventional restoration [CR]) in a 5-y randomized controlled practice-based trial in Scotland. We interrogated this data set further to investigate the cost-effectiveness of HT versus CR. A total of 132 children who had 2 matched occlusal/occlusal-proximal carious lesions in primary molars ( n = 264 teeth) were randomly allocated to HT or CR, provided by 17 general dental practitioners. Molars were followed up for a mean 5 y. A societal perspective was taken for the economic analysis. Direct dental treatment costs were estimated from a Scottish NHS perspective (an NHS England perspective was taken for a sensitivity analysis). Initial, maintenance, and retreatment costs, including rerestorations, endodontic treatments, and extractions, were estimated with fee items. Indirect/opportunity costs were estimated with time and travel costs from a UK perspective. The primary outcome was tooth survival. Secondary outcomes included 1) not having pain or needing endodontic treatments/extractions and 2) not needing rerestorations. Cost-effectiveness and acceptability were estimated from bootstrapped samples. Significantly more molars in HT survived (99%, 95% CI: 98% to 100%) than in CR (92%; 87% to 97%). Also, the proportion of molars retained without pain or requiring endodontic treatment/extraction was significantly higher in HT than CR. In the base case analysis (NHS Scotland perspective), cumulative direct dental treatment costs (Great British pound [GBP]) of HT were 24 GBP (95% CI: 23 to 25); costs for CR were 29 (17 to 46). From an NHS England perspective, the cost advantage of HT (29 GBP; 95% CI: 25 to 34) over CR (107; 86 to 127) was more pronounced. Indirect/opportunity costs were significantly lower for HT (8 GBP; 95% CI: 7 to 9) than CR (19; 16 to 23). Total cumulative costs were significantly lower for HT (32 GBP; 95% CI: 31 to 34) than CR (49; 34 to 69). Based on a long-term practice-based trial, HT was more cost-effective than CR with HT retained for longer and experiencing less complications at lower costs.

Background: Hip, vertebral and wrist fractures are the most common consequences of osteoporosis. This study aimed at analyzing the cost-effectiveness of teriparatide (CinnoPar®), compared with alendronate and risedronate, in the treatment of women aged 60 and over with postmenopausal osteoporosis in Iran. Methods: A decision tree model with a 2-year time horizon was used to compare treatment with teriparatide (CinnoPar®) with the following treatment strategies: two years of treatment with alendronate and two years of treatment with risedronate in women aged 60 years and over or those at risk of osteoporosis. Cost per QALY was calculated for 3 treatment strategies from the model. After base case analysis, one-way sensitivity analysis was performed on key parameters of the model to assess their impact on the study results and the cost-effectiveness of different treatment strategies and the model robustness. TreeAge Pro 2006 software was used for modeling and data analysis. Results: Incremental cost-effectiveness ratio (ICER) of alendronate and teriparatide than risedronate (base treatment) were US$- 2178.03 and US$483,783.67 per QALY, respectively. Therefore, the dominant and cost-effective treatment option was alendronate. In the one-way sensitivity analysis, the impact of annual 25% increase or decrease in the teriparatide cost on its ICER was remarkable. Also, reducing the discount rate from 0.03 to 0.0 had the greatest impact on the ICER of the teriparatide. Conclusion: The treatment strategy of teriparatide is more expensive than risedronate and alendronate and is associated with very little increase in QALYs. A significant reduction in teriparatide price and a limit in its use only for high-risk women and for acute and short-term treatment courses can contribute to its cost-effectiveness.

We evaluated the cost-effectiveness of a gadoxetic acid-enhanced MRI (EOB-MRI) strategy compared with conventional MRI strategy and biopsy to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). A decision tree model was constructed to compare the cost-effectiveness of EOB-MRI, conventional MRI with extracellular contrast agents, and biopsy as the initial diagnostic modality in patients with incidentally detected focal liver lesions suspected of being FNH or HCA. We analysed the cost and effectiveness, i.e. probability of successful diagnosis of each strategy. Costs were based on utilisation rates and Medicare reimbursements in the USA and South Korea. In the base case analysis of our decision tree model, the effectiveness of the three strategies was similar. The cost of the EOB-MRI strategy ($1283 in USA, $813 in South Korea) was lowest compared with the biopsy strategy ($1725 in USA, $847 in South Korea) and the conventional MRI strategy ($1750 in USA, $962 in South Korea). One-way, two-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. EOB-MRI strategy is the most cost-effective strategy for differentiating FNH from HCA in patients with incidentally detected focal liver lesions in a non-cirrhotic liver. • The effectiveness of the three strategies was similar. • The cost of the EOB-MRI strategy was lowest. • EOB-MRI strategy is the most cost-effective for differentiating FNH from HCA.

Information and communications technology (ICT)/cyber technologies become ever-more embedded in our economies and societies, bringing both benefits and risk-related costs. The balance between those benefits and costs, over time and across countries, remains poorly understood. This gives rise to conflicting narratives about the future of ICT: either (1) continued rapid benefit growth with new waves of ICT technology; or (2) increasing cyber-attack costs will come to swamp benefits. We explore how the balance between benefits and costs might change at the global, country-grouping, and country-level out to 2030. Because the existing literature provides little foundation for integrated analysis, we did extensive conceptual research and data gathering from diverse sources. The benefits include the growth of the ICT sector itself, its contribution to broader productivity as a general purpose technology, and its benefits for consumers as value for price rises very significantly. The costs include security spending, the impact of adverse cyber events, and opportunity foregone if the technology is underutilized. We extended International Futures (IFs), an existing multi-issue, multi-country, long-term forecasting system with formulations driving ICT/cyber advance and impact. In Base Case analysis we found that, while annual costs related to cyber-attacks and cyber-security spending do come to outweigh the annual incremental economic benefits from ICT use in high-income countries, over time the compounding nature of the benefits versus the more additive nature of the costs means that the cumulative benefits will outstrip the cumulative costs by tens of trillions of dollars over even medium-term forecast horizons. For lower-income and middle-income countries both annual and cumulative analyses suggest that benefits will continue to outweigh costs. On a global basis the cumulative net benefits could exceed $100 trillion through 2030. Four scenarios with significantly different assumptions about technological development and the unfolding of adverse events changed the total values of benefits and risk-related costs, but not the overall conclusion.

Objective:In most settings, less than 25% of patients with treatment-resistant schizophrenia receive clozapine, the only medication proven effective for treatment-resistant schizophrenia. Therefore, a business case analysis was conducted to assess whether increasing clozapine utilization for treatment-resistant schizophrenia in a health care system would result in direct health care cost savings.Methods:Veterans with treatment-resistant schizophrenia who were treated in the Veterans Health Administration (VHA) were studied. Treatment response, suicides, adverse drug reactions (and associated mortality), and effects on inpatient hospitalization related to clozapine were derived from a systematic review of published studies. A one-factor sensitivity analysis and a probabilistic sensitivity analysis (PSA) with Monte Carlo simulation were conducted to calculate the cost-benefits of increased clozapine utilization.Results:Despite monitoring costs, in the base case analysis, the VHA would save $22,444 per veter...

Introduction: Three pivotal trials have considered the addition of docetaxel (D) chemotherapy to conventional androgen-deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (HSPC). While an initial small trial was inconclusive, two larger trials demonstrated significant clinical benefit, including pronounced survival benefits (added 17 months) among patients with high-volume metastatic disease. Given the evolving clinical evidence, the cost-effectiveness of this approach warrants exploration. Methods: The cost-effectiveness of six cycles of ADT+D compared to ADT alone to treat patients with high-volume metastatic HSPC was assessed from a Canadian public payer perspective. We included three health states: HSPC, metastatic castration-resistant prostate cancer (CRPC), and death. Survival data were obtained from the CHAARTED trial, which reported outcomes specifically for high-volume disease. We used Ontario costs data and utilities from the literature. Results: In the base case analysis, ADT+D cost an additional $25 757 and produced an extra 1.06 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of $24 226/QALY gained. Results from one-way sensitivity analysis across wide ranges of estimates and a range of scenarios, including an alternate model structure, produced ICERs below $35 000/QALY gained in all cases. Conclusions: The use of D with ADT in high-volume metastatic HSPC appears to be an economically attractive treatment approach. The findings were consistent with other studies and robust in sensitivity analysis across a variety of scenarios.

Objective.The 2012 American College of Rheumatology gout management guidelines recommend monitoring serum urate (SU) every 6 months after target SU has been achieved. Our objective was to determine through modeling whether this testing would be cost-effective, considering financial cost, quality of life, and estimated change in adherence.Methods.A cost-utility analysis was completed with a 3-arm model: (1) no regular urate monitoring; (2) annual urate monitoring; and (3) biannual urate monitoring. Inputs to the model for health-related quality of life, flare rate, and treatment location were drawn from the medical literature and modeled over a lifetime horizon.Results.No monitoring was the least costly (Australian$6974) but least effective [13.51 quality-adjusted life-yrs (QALY)], while annual urate monitoring [A$7117; 13.53 QALY; incremental cost-effectiveness ratio (ICER) A$13,678/QALY gained] and biannual monitoring [A$7298; 13.54 QALY; ICER A$15,420 per QALY gained] were both cost-effective alternatives in base case analysis. Sensitivity analysis on both an individual component level and a probabilistic sensitivity analysis (PSA) demonstrated that the result was robust to changes in input variables. An improvement in adherence of ≥ 3.5% with biannual monitoring was all that was required to demonstrate cost-effectiveness. In PSA, the probability of biannual monitoring was 78%, no monitoring was 20%, and annual monitoring was 2%.Conclusion.The results suggest that biannual SU monitoring after attaining target SU is the most cost-effective, compared with no testing and annual testing.

Retrievable inferior vena cava (IVC) filters were first approved for use in the United States in 2003 to address the long-term complications of migration, thrombosis, fracture, and perforation observed with permanent IVC filter implantation. Although Food and Drug Administration approval of retrievable IVC filters includes permanent implantation, the incidence of complications from long-term implantation appears to be greater than that reported with existing permanent IVC filters. Also, only a small fraction of such retrievable IVC filters are ever retrieved. The purpose of the present study was to determine the threshold retrieval rate at which the use of retrievable IVC filters could be justified.A Markov decision tree was constructed comparing retrievable and permanent IVC filters regarding their effectiveness and cost. A review of the reported data provided outcome probabilities, and the Tufts Medical Center Cost-Effectiveness Analysis Registry was the source of the utility values for the various potential outcomes. Medicare reimbursement rates served as a proxy for costs. A sensitivity analysis was performed for various parameters, primarily to determine the retrieval rate threshold at which the use of retrievable IVC filters would outperform the use of permanent IVC filters.Base case analysis demonstrated a greater predicted effectiveness for permanent compared with retrievable IVC filter implantation (5.41 quality-adjusted life-years [QALY] vs 5.33 QALY) at a lower cost ($2070 vs $4650). Monte Carlo simulation at 10,000 iterations confirmed the expected utility (5.4 ± 3.0 QALY vs 5.3 ± 3.0 QALY; P = .0002) and cost ($1900 ± $7400 vs $4800 ± 9900; P .0001) to be statistically superior for permanent IVC filters. A sensitivity analysis for the filter retrieval rate demonstrated that the strategy of using a retrievable IVC filter was never preferable for utility or cost. The superiority of permanent IVC filter placement for effectiveness and cost persisted, regardless of anticipated patient-predicted annual mortality. A two-way sensitivity analysis for both IVC filter removal rate and annual patient mortality confirmed the superiority of permanent IVC filter placement at all levels.The predicted effectiveness of permanent IVC filters was greater and the predicted cost lower than those for retrievable IVC filters, regardless of the IVC filter retrieval rate. This interpretation of existing reported data using Markov decision analysis modeling supports the argument that unless the long-term complication rate of retrievable IVC filters can be significantly improved, their use should be abandoned in favor of currently available permanent IVC filters.

Background and Objective. Bacterial resistance to antibiotics traditionally used to treat uncomplicated urinary tract infections (uUTIs) is rising in Canada. We compared the cost-per-patient in Ontario of including fosfomycin (an antibiotic with a low resistance profile) as an option for first-line empirical treatment of uUTIs with current cost of treatment with sulfonamides, fluoroquinolones, and nitrofurantoin.Methods. A decision-tree model was used to perform a cost-minimization analysis. All possible outcomes of a uUTI caused by bacterial species treated with either sulfonamides, fluoroquinolones, nitrofurantoin, or fosfomycin were included.Results. In the base case analysis, the cost-per-patient for treating uUTI with fosfomycin was $105.12. This is similar to the cost-per-patient for each of the other currently reimbursed antibiotics (e.g., $96.19 for sulfonamides, $98.85 for fluoroquinolones, and $99.09 for nitrofurantoins). The weighted average cost-per-patient for treating uUTI was not substantially elevated with the inclusion of fosfomycin in the treatment landscape ($98.41 versus $98.29 with and without fosfomycin, resp.). The sensitivity analyses revealed that most (88.34%) of the potential variation in cost was associated with the probability of progressing to pyelonephritis and hospitalization for pyelonephritis.Conclusion. Fosfomycin in addition to being a safe and effective agent to treat uUTI has a low resistance profile, offers a single-dose treatment administration, and is similar in cost to other reimbursed antibiotics.

Objectives To compare the costs of photoselective vaporisation (PVP) and transurethral resection of the prostate (TURP) for management of symptomatic benign prostatic hyperplasia (BPH) from the perspective of a Queensland public hospital provider. Patients and Methods A decision-analytic model was used to compare the costs of PVP and TURP. Cost inputs were sourced from an audit of patients undergoing PVP or TURP across three hospitals. The probability of re-intervention was obtained from secondary literature sources. Probabilistic and multi-way sensitivity analyses were used to account for uncertainty and test the impact of varying key assumptions. Results In the base case analysis, which included equipment, training and re-intervention costs, PVP was AU$ 739 (95% credible interval [CrI] –12 187 to 14 516) more costly per patient than TURP. The estimate was most sensitive to changes in procedural costs, fibre costs and the probability of re-intervention. Sensitivity analyses based on data from the most favourable site or excluding equipment and training costs reduced the point estimate to favour PVP (incremental cost AU$ –684, 95% CrI –8319 to 5796 and AU$ –100, 95% CrI –13 026 to 13 678, respectively). However, CrIs were wide for all analyses. Conclusions In this cost minimisation analysis, there was no significant cost difference between PVP and TURP, after accounting for equipment, training and re-intervention costs. However, PVP was associated with a shorter length of stay and lower procedural costs during audit, indicating PVP potentially provides comparatively good value for money once the technology is established.

Purpose To undertake a quantitative benefit–risk analysis of rofecoxib relative to naproxen using an incremental net-benefit (INB) analysis from the societal perspective, using the same data evaluated by the Health Canada and US FDA expert advisory panels. Methods We developed a discrete event simulation model to calculate the INB of rofecoxib relative to naproxen in arthritis patients over a 1-year time horizon. All outcomes were weighted using societal utilities for each health state which facilitated the use of quality-adjusted life years (QALYs) as the outcome. Probability distributions were incorporated for each model parameter to facilitate a probabilistic analysis using second-order Monte Carlo simulation. Results In the base case analysis, the mean INB (SD) of rofecoxib relative to naproxen was 0.0002 (0.415) QALYs per patient over 12 months of treatment, or 0.2 QALYs per 1000 patients treated. The probabilistic sensitivity analysis resulted in a mean INB of 0.0022 QALYs (95%CI −0.0005, 0.0051). Overall, the INB associated with rofecoxib relative to naproxen was ≥0 in 94% of the iterations of the model. Conclusions This analysis illustrates the application of the incremental net-benefit framework to quantitative benefit–risk evaluation, and suggests that the potential benefits of rofecoxib outweigh the potential harms relative to naproxen over 1 year from the societal perspective under the assumptions of this model. Copyright © 2010 John Wiley & Sons, Ltd.

We illustrate a methodology for estimating the damages to commercial fisheries from entrainment and from temporary loss of seafloor habitat productivity because of marine sand mining. A Beverton-Holt, year-class model is used to estimate illustrative short-term, long-term, and indirect (food web) effects from the inception of mining through the time to recovery of the injured resource stocks. A Base Case analysis evaluates hypothetical mining for a 4 km 2 mining site with biological recovery of the mined area beginning seven months after mining ceases and the bottom excavation fills in. Sensitivity analyses also are used to illustrate damages for alternative recovery paths and for 20 hypothetical mining sites for one year of mining and for recurring mining for 5 and for 10 years. Important qualifications and directions for further research are outlined.

Background. Composite tissue allotransplantation (CTA) represents a surgical technology whose risks and benefits are unclear. This is problematic for clinicians with respect to patient selection and counseling, and for policy makers in evaluating its merits. Our analysis represents a mathematical approach to risk and benefit estimation in CTA. Methods. A Markov model was created to represent clinical and immunological outcomes after CTA. Esthetic outcomes were incorporated into the model by creating a disfigurement-related-disability severity score index based on existing literature. Composite tissue allotransplantation in a 30-year-old male was used as a base case analysis. We compared CTA against autogenous reconstruction as competing strategies. Sensitivity analyses were performed on the effect of preoperative esthetic morbidity and postoperative esthetic outcome. Results. Our base-case showed CTA to be the preferred strategy-conferring a benefit of 4.47 esthetic-outcome-adjusted life years. Sensitivity analyses showed CTA to be the preferred strategy if the preoperative disability severity score was greater than 5, and if the severity score after autogenous reconstruction was greater than 7. Conclusion. Our model estimates a theoretical risk-benefit threshold for CTA. The model itself can be refined as clinical experience with CTA grows and can incorporate economic and quality-of-life parameters.

Because all important assumptions used in the model are simultaneously biased toward PCV10, the model results are erroneous and misleading. Routine infant pneumococcal vaccination in Japan would undoubtedly bring substantial reductions in morbidity and mortality. However, given the current epidemiologic landscape in Japan and the current evidence, the clinical and economic gains from the use of PCV13 would, undoubtedly, far exceed those potentially observed from the use of PCV10. We urge those who conduct, critique, and consider cost-effectiveness studies to evaluate the strength of the evidence of clinical claims for the products and the influence these assumptions have on the overall findings. In addition, when performing economic predictive modeling, it is critical to provide a balanced perspective by weighing the strengths and weaknesses of all available data to construct the base case analysis.

The CISNET breast cancer program is a consortium of seven research groups modeling the impact of various cancer interventions on the national trends of breast cancer incidence and mortality. Each of the modeling groups participated in a CISNET breast cancer base case analysis with the objective of assessing the impact of mammography and adjuvant therapy on breast cancer mortality between 1975 and 2000. The comparative modeling approach used to address this question allowed for a unique view into the process of modeling. Results shown here expand on those recently reported in the New England Journal of Medicine (Berry et al., N Engl J Med 2005;353:1784-92) by presenting mortality impact in several different ways to facilitate comparisons between models. Comparisons of each group's results in the context of modeling assumptions made during the process gave insight into how specific model assumptions may have affected the results. The median estimate for the percent decline in breast cancer mortality due to mammography was 15% (range of 8%-23%), and the median estimate for the percent decline in mortality due to adjuvant treatment was 19% (range of 12%-21%). A detailed discussion of the differences in modeling approaches and how those differences may have influenced the mortality results concludes the chapter.

Objective To determine the cost-effectiveness of the newer antiseptic and antibiotic-impregnated central venous catheters (CVCs) relative to uncoated CVCs and to each other. Design Decision model analysis of the cost and efficacy of CVCs coated with either chlorhexidine silver sulfadiazine (CSS) or rifampin-minocycline (RM) at preventing catheter-related bloodstream infections (CRBSIs). The primary outcome is the incremental cost (or savings) to prevent one additional CRBSI. Model estimates are derived from prospective trials of the CSS and RM CVCs and from other studies describing the costs of CRBSIs. Setting and patients Hypothetical cohort of 1,000 patients requiring placement of a CVC. Interventions In the model, patients were managed with either an uncoated CVC, CSS CVC, or RM CVC. Measurements and main results The incremental cost-effectiveness of the treated CVCs was calculated as the savings resulting from CRBSIs averted less the additional costs of the newer devices. Sensitivity analysis of the effect of the major clinical inputs was performed. For the base case analysis, we assumed the incidence of CRBSIs was 3.3% with traditional catheters and that the CSS and RM CVC conferred a relative risk reduction for the development of CRBSIs of 60% and 85%, respectively. Despite their significantly higher cost than older catheters, both novel CVCs yield significant savings. Employing either of the treated CVCs saves approximately $10,000 per CRBSI prevented (relative to standard catheters). Comparing the RM CVC to the CSS CVC revealed the RM product to be economically superior, saving nearly $9,600 per CRBSI averted and $81 per patient in the cohort. For sensitivity analysis, we adjusted all model variables by 50% individually and then simultaneously. This demonstrated the model to be most sensitive to the cost of a CRBSI; however, with all inputs skewed by 50% against both the CSS CVC and the RM CVC, these devices remained economically attractive. Under this scenario, use of either treated device was less costly. Conclusions Utilization of antiseptic and antibiotic-impregnated CVCs represent an attractive alternative for the prevention of CRBSIs and may lead to significant savings. Of the two newer, coated devices, the RM CVC performs better financially. These observations hold over a range of estimates for our model inputs.

Telepathology is gaining acceptance as a mode of providing pathology services to remote sites, but its economic feasibility is unknown. A dynamic robotic telepathology service between the Veterans Affairs Medical Center, Iron Mountain, MI, and the Veterans Affairs Medical Center, Milwaukee, WI, provides diagnostic services for routine and frozen section surgical pathology cases at Iron Mountain. We conducted a cost minimization analysis of this service by building a model to compare telepathology and on-site pathology in Iron Mountain and a courier method of transporting specimens from Iron Mountain to Milwaukee for diagnosis. Base case analysis showed the courier method to be the most economic; telepathology was less costly than on-site pathology. If the costs of telepathology equipment and telecommunication are lowered to reflect current cost, then telepathology becomes the favored option. Telepathology can be an economic mode of providing pathology services to a remote site.

Purpose: To use Normal Tissue Complication Probability (NTCP) models and comparative planning studies to explore the (cost-) effectiveness of swallowing sparing intensity modulated proton radiotherapy (IMPT) compared with swallowing sparing intensity modulated radiotherapy with photons (IMRT) in head and neck cancer (HNC).Methods and Materials: A Markov model was constructed to examine and compare the costs and quality-adjusted life years (QALYs) of the following strategies: (1) IMPT for all patients; (2) IMRT for all patients; and (3) IMPT if efficient. The assumption of equal survival for IMPT and IMRT in the base case analysis was relaxed in a sensitivity analysis.Results: Intensity modulated proton radiation therapy and IMRT for all patients yielded 6.620 and 6.520 QALYs and cost (sic)50,989 and (sic)41,038, respectively. Intensity modulated proton radiation therapy if efficient yielded 6.563 QALYs and cost (sic)43,650. The incremental cost-effectiveness ratio of IMPT if efficient versus IMRT for all patients was (sic)60,278 per QALY gained. In the sensitivity analysis, IMRT was more effective (0.967 QALYs) and less expensive ((sic)8218) and thus dominated IMPT for all patients.Conclusions: Cost-effectiveness analysis based on normal tissue complication probability models and planning studies proved feasible and informative and enables the analysis of individualized strategies. The increased effectiveness of IMPT does not seem to outweigh the higher costs for all head-and-neck cancer patients. However, when assuming equal survival among both modalities, there seems to be value in identifying those patients for whom IMPT is cost-effective. (C) 2013 Elsevier Inc.

Objective To compare the cost-effectiveness of four, six, and eight doses per month of vardenafil in the context of pharmacy benefit decision making. Methods A Markov model was used to estimate the incremental cost-effectiveness of zero, four, six, or eight doses of vardenafil per month in hypothetical cohorts of 60-year-old male veterans with erectile dysfunction. Efficacy values for vardenafil were obtained from the literature, and vardenafil costs were obtained from Veterans Affairs pharmacy data. The analysis was conducted from a third-party payer perspective with a lifetime horizon, and the effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. Results In the base case analysis, the cost per quality-adjusted life-year gained for four doses of vardenafil per month compared with no therapy was $576. Six doses per month compared with four cost $2585/quality-adjusted life-year gained, and eight doses per month compared with six cost $5169/quality-adjusted life-year gained. In one-way sensitivity analyses of six doses per month compared with four, variation of two parameters caused the incremental cost-effectiveness ratio to cross a willingness-to-pay threshold of $20,000: when the increased utility associated with giving two additional doses/month was less than 0.001 (baseline 0.01) and when the cost per dose increased to $15.00 (baseline $1.69). Conclusion Although four doses per month of vardenafil was the most cost-effective strategy, the use of six or eight doses per month also compares favorably with other accepted medical treatments. The results were stable across a range of inputs and help to support the current Veterans Affairs policy on the number of vardenafil doses provided per month for erectile dysfunction.

Background Recent data have shown that type 2 diabetes patients in the UK delay initiating insulin on average for over 11 years after first being prescribed an oral medication. Using a published computer simulation model of diabetes we used UK-specific data to estimate the clinical consequences of immediately initiating insulin versus delaying initiation for periods in line with published estimates. Methods In the base case scenario simulated patients, with characteristics based on published UK data, were modelled as either initiating insulin immediately or delaying for 8 years. Clinical outcomes in terms of both life expectancy and quality-adjusted life expectancy and also diabetes-related complications (cumulative incidence and time to onset) were projected over a 35 year time horizon. Treatment effects associated with insulin use were taken from published studies and sensitivity analyses were performed around time to initiation of insulin, insulin efficacies and hypoglycaemia utilities. Results For patients immediately initiating insulin there were increases in (undiscounted) life expectancy of 0.61 years and quality-adjusted life expectancy of 0.34 quality-adjusted life years versus delaying initiation for 8 years. There were also substantial reductions in cumulative incidence and time to onset of all diabetes-related complications with immediate versus delayed insulin initiation. Sensitivity analyses showed that a reduced delay in insulin initiation or change in insulin efficacy still demonstrated clinical benefits for immediate versus delayed initiation. Conclusion UK type 2 diabetes patients are at increased risk of a large number of diabetes-related complications due to an unnecessary delay in insulin initiation. Despite clear guidelines recommending tight glycaemic control this failure to begin insulin therapy promptly is likely to result in needlessly reduced life expectancy and compromised quality of life.

Objectives: Spinal cord stimulation (SCS) has been used for almost 40 years to treat refractory neuropathic pain after failed back surgery. Fully implantable nonrechargeable pulse generators have a battery life of between 2 and 5 years. A new SCS system with a rechargeable power source may last 10 to 25 years, or longer. The potential economic implications of longer battery life with a new SCS system has yet to be assessed. The study objective is to estimate the average difference in lifetime costs between rechargeable and nonrechargeable pulse generators used in treatment with SCS for failed back surgery syndrome. Methods: A generalized state-transition probability framework was used to model costs. Input parameters for the base case analysis were obtained from several data sources including published literature, Medicare fee schedules, Medicare claims data, and expert opinion. Results: A rechargeable SCS system is projected to require from 2.6 to 4.2 fewer battery generator replacements for battery depletion than a nonrechargeable SCS system. The total lifetime savings of a rechargeable system range from $104,000 to $168,833. In all of the one-way sensitivity analyses conducted, a rechargeable system saves money. Among all of the assumptions underlying the analysis, the annual cost after device removal contributes the most uncertainty. Conclusions: A rechargeable SCS system is projected to save up to $100,000 over a patient’s lifetime. Fewer pulse generator replacements will also decrease patient discomfort and morbidity from procedural complications.

literature to compare current standard approach using tapered vancomycin to FMT for rCDI [Figure 1]. Values used include cure rates for vancomyin and FMT, 69% (range:59-75%) and 91% (range:83-100%), respectively. The direct cost of vancomycin and FMT, adjusted to 2011 dollars, were $2069 (range: $1836-2303) and $951 ($713-1189), respectively [Table 1]. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. Analysis was performed from the third-party payer perspective and one-way and probabilistic sensitivity analyses were conducted. RESULTS: Base case analysis showed that FMT is less costly ($1,378 vs. $3,248) and more effective (0.242 QALYs vs. 0.235 QALYs) than vancomycin for rCDI . One-way sensitivity analyses showed that FMTwas the dominant strategy (both less expensive and more effective) as long as the cure rates for FMT and vancomycin were at least 70% and less than 91%, respectively, and if the cost of FMT was less than $2822. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy in all 10,000 2nd order Monte Carlo simulations. CONCLUSION: Our results suggest that FMT may be a cost-saving intervention in managing recurrent Clostridium difficile infections. Implementation of FMT for rCDI may help decrease the economic burden to the healthcare system. Model Variables

sus CCAB was $Can (−) 131,260 per QALY gained in the base case analysis, suggesting a significant cost savings to the health care system per QALY gained when OPCAB was performed rather than CCAB. The ICER was similar when institutional and societal perspectives were taken. The ICER remained robust across extensive sensitivity analyses. Conclusion. Off-pump coronary artery bypass appears to be a cost-saving alternative to conventional coronary artery bypass in CAD patients presenting for surgical revascularisation. The estimated ICER was robust across plausible ranges of assumptions and from a variety of perspectives, suggesting that OPCAB should be considered cost-saving to the healthcare system, the acute care hospital, and to society.

The current national policy to manage nuclear waste from power plants is to dispose of it in a repository to be constructed at Yucca Mountain in Nevada. With many different assumptions about uncertainties and objectives, this strategy is shown to be the equivalent of $10,000 million to $50,000 million inferior to other available strategies. The implications of the analysis strongly suggest that our national policy to manage nuclear waste should be changed.

Objective To determine the cost-effectiveness of the newer antiseptic and antibiotic-impregnated central venous catheters (CVCs) relative to uncoated CVCs and to each other. Design Decision model analysis of the cost and efficacy of CVCs coated with either chlorhexidine silver sulfadiazine (CSS) or rifampin-minocycline (RM) at preventing catheter-related bloodstream infections (CRBSIs). The primary outcome is the incremental cost (or savings) to prevent one additional CRBSI. Model estimates are derived from prospective trials of the CSS and RM CVCs and from other studies describing the costs of CRBSIs. Setting and patients Hypothetical cohort of 1,000 patients requiring placement of a CVC. Interventions In the model, patients were managed with either an uncoated CVC, CSS CVC, or RM CVC. Measurements and main results The incremental cost-effectiveness of the treated CVCs was calculated as the savings resulting from CRBSIs averted less the additional costs of the newer devices. Sensitivity analysis of the effect of the major clinical inputs was performed. For the base case analysis, we assumed the incidence of CRBSIs was 3.3% with traditional catheters and that the CSS and RM CVC conferred a relative risk reduction for the development of CRBSIs of 60% and 85%, respectively. Despite their significantly higher cost than older catheters, both novel CVCs yield significant savings. Employing either of the treated CVCs saves approximately $10,000 per CRBSI prevented (relative to standard catheters). Comparing the RM CVC to the CSS CVC revealed the RM product to be economically superior, saving nearly $9,600 per CRBSI averted and $81 per patient in the cohort. For sensitivity analysis, we adjusted all model variables by 50% individually and then simultaneously. This demonstrated the model to be most sensitive to the cost of a CRBSI; however, with all inputs skewed by 50% against both the CSS CVC and the RM CVC, these devices remained economically attractive. Under this scenario, use of either treated device was less costly. Conclusions Utilization of antiseptic and antibiotic-impregnated CVCs represent an attractive alternative for the prevention of CRBSIs and may lead to significant savings. Of the two newer, coated devices, the RM CVC performs better financially. These observations hold over a range of estimates for our model inputs.

Aim: To compare the costs of midazolam and droperidol for the management of acute agitation in the emergency department (ED). Method: A decision analysis model was used to undertake a cost-minimisation analysis of resource utilisation in the ED of a Melbourne hospital. Data from acutely agitated patients who received midazolam (n = 74) or droperidol (n = 79) in a randomised clinical trial (February 2002 to April 2004) were reviewed. Results: All direct medical and non-medical costs relating to the management of acute agitation in the ED were analysed. The average cost scenario was estimated for the 2 treatments. The model simulated 9 possible outcomes based on whether patients were ‘sedated’ or ‘not sedated’ and whether they required ‘re-dosing’ or ‘no re-dosing’. Hospitalisation cost incorporated multiple items as part of the average cost per service code for the ED length of stay. In the base case analysis, midazolam was associated with notably less overall drug costs (A$3.05 vs A$21.10), which contributed to less total treatment costs. The ‘expected’ median ED length of stay was marginally longer in the midazolam group (12 vs 11.8 hours), resulting in slightly higher hospitalisation costs (A$1370 vs A$1361). The midazolam group incurred higher median costs for pathology (A$78.60 vs A$61.60) and imaging (A$5.25 vs A$0.60). The cost of electrocardiograms was similar (A$27.10 vs A$28). With a cost advantage of A$59 per patient, midazolam was 3.8% less costly than droperidol (A$1496 vs A$1555). Conclusion: Midazolam was marginally more cost saving than droperidol when used to manage acute agitation in the ED. Several challenges were identified that need to be overcome to enable future robust pharmacoeconomic studies. J Pharm Pract Res 2012; 42: 11-16.