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1.  Cost-effectiveness analysis of human papillomavirus DNA testing and Pap smear for cervical cancer screening in a publicly financed health-care system 
British Journal of Cancer  2010;103(12):1773-1782.
Objective:
To evaluate the long-term cost-effectiveness of different strategies for human papillomavirus (HPV) DNA testing combined with Pap smear for cervical cancer screening in Taiwan.
Methods:
This study adopts a perspective of Department of Health in cost-effectiveness analysis to compare a no-screening strategy with nine different screening strategies. These strategies comprise three screening tools (Pap smear alone, HPV DNA testing followed by Pap smear triage, and HPV DNA testing combined with Pap smear), and three screening intervals (annually, every 3 years, and every 5 years). Outcomes are life expectancy, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analyses (PSAs) were conducted to assess parameter uncertainty.
Results:
When three times gross domestic product per capita is used as the decision threshold, all nine screening strategies were cost-effective compared with the no-screening strategy. Compared with the current screening strategy (an annual Pap smear), HPV DNA testing followed by Pap smear triage every 5 years and every 3 years were cost-effective. Results of PSA also indicated that a HPV DNA testing followed by Pap smear triage every 5 or every 3 years achieved the highest expected net benefits.
Conclusions:
Possible economic advantages are associated with extending the cervical cancer screening interval from one Pap smear annually to HPV DNA testing followed by Pap smear triage every 5 years with an ICER $1 247 000 per QALY gained, especially in a country with a publicly financed health-care system.
doi:10.1038/sj.bjc.6605974
PMCID: PMC3008604  PMID: 21102588
HPV DNA testing; Pap smear; cost-effectiveness analysis; cervical cancer; screening
2.  An Assessment of Japanese Carbon Tax Reform Using the E3MG Econometric Model 
The Scientific World Journal  2012;2012:835917.
This paper analyses the potential economic and environmental effects of carbon taxation in Japan using the E3MG model, a global macroeconometric model constructed by the University of Cambridge and Cambridge Econometrics. The paper approaches the issues by considering first the impacts of the carbon tax in Japan introduced in 2012 and then the measures necessary to reduce Japan's emissions in line with its Copenhagen pledge of −25% compared to 1990 levels. The results from the model suggest that FY2012 Tax Reform has only a small impact on emission levels and no significant impact on GDP and employment. The potential costs of reducing emissions to meet the 25% reduction target for 2020 are quite modest, but noticeable. GDP falls by around 1.2% compared to the baseline and employment by 0.4% compared to the baseline. But this could be offset, with some potential economic benefits, if revenues are recycled efficiently. This paper considers two revenue recycling scenarios. The most positive outcome is if revenues are used both to reduce income tax rates and to increase investment in energy efficiency. This paper shows there could be double dividend effects, if Carbon Tax Reform is properly designed.
doi:10.1100/2012/835917
PMCID: PMC3530177  PMID: 23365531
3.  Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis 
PLoS ONE  2012;7(8):e40808.
Background
The PACE trial compared the effectiveness of adding adaptive pacing therapy (APT), cognitive behaviour therapy (CBT), or graded exercise therapy (GET), to specialist medical care (SMC) for patients with chronic fatigue syndrome. This paper reports the relative cost-effectiveness of these treatments in terms of quality adjusted life years (QALYs) and improvements in fatigue and physical function.
Methods
Resource use was measured and costs calculated. Healthcare and societal costs (healthcare plus lost production and unpaid informal care) were combined with QALYs gained, and changes in fatigue and disability; incremental cost-effectiveness ratios (ICERs) were computed.
Results
SMC patients had significantly lower healthcare costs than those receiving APT, CBT and GET. If society is willing to value a QALY at £30,000 there is a 62.7% likelihood that CBT is the most cost-effective therapy, a 26.8% likelihood that GET is most cost effective, 2.6% that APT is most cost-effective and 7.9% that SMC alone is most cost-effective. Compared to SMC alone, the incremental healthcare cost per QALY was £18,374 for CBT, £23,615 for GET and £55,235 for APT. From a societal perspective CBT has a 59.5% likelihood of being the most cost-effective, GET 34.8%, APT 0.2% and SMC alone 5.5%. CBT and GET dominated SMC, while APT had a cost per QALY of £127,047. ICERs using reductions in fatigue and disability as outcomes largely mirrored these findings.
Conclusions
Comparing the four treatments using a health care perspective, CBT had the greatest probability of being the most cost-effective followed by GET. APT had a lower probability of being the most cost-effective option than SMC alone. The relative cost-effectiveness was even greater from a societal perspective as additional cost savings due to reduced need for informal care were likely.
doi:10.1371/journal.pone.0040808
PMCID: PMC3411573  PMID: 22870204
4.  Cost-effectiveness of a programme of screening and brief interventions for alcohol in primary care in Italy 
BMC Family Practice  2014;15:26.
Background
As alcohol-related health problems continue to rise, the attention of policy-makers is increasingly turning to Screening and Brief Intervention (SBI) programmes. The effectiveness of such programmes in primary healthcare is well evidenced, but very few cost-effectiveness analyses have been conducted and none which specifically consider the Italian context.
Methods
The Sheffield Alcohol Policy Model has been used to model the cost-effectiveness of government pricing and public health policies in several countries including England. This study adapts the model using Italian data to evaluate a programme of screening and brief interventions in Italy. Results are reported as Incremental Cost-Effectiveness Ratios (ICERs) of SBI programmes versus a ‘do-nothing’ scenario.
Results
Model results show such programmes to be highly cost-effective, with estimated ICERs of €550/Quality Adjusted Life Year (QALY) gained for a programme of SBI at next GP registration and €590/QALY for SBI at next GP consultation. A range of sensitivity analyses suggest these results are robust under all but the most pessimistic assumptions.
Conclusions
This study provides strong support for the promotion of a policy of screening and brief interventions throughout Italy, although policy makers should be aware of the resource implications of different implementation options.
doi:10.1186/1471-2296-15-26
PMCID: PMC3936801  PMID: 24502342
Public health interventions; Alcohol; Primary care; Cost-effectiveness
5.  Cost effectiveness analysis of population-based serology screening and 13C-Urea breath test for Helicobacter pylori to prevent gastric cancer: A markov model 
AIM: To compare the costs and effectiveness of no screening and no eradication therapy, the population-based Helicobacter pylori (H pylori) serology screening with eradication therapy and 13C-Urea breath test (UBT) with eradication therapy.
METHODS: A Markov model simulation was carried out in all 237 900 Chinese males with age between 35 and 44 from the perspective of the public healthcare provider in Singapore. The main outcome measures were the costs, number of gastric cancer cases prevented, life years saved, and quality-adjusted life years (QALYs) gained from screening age to death. The uncertainty surrounding the cost-effectiveness ratio was addressed by one-way sensitivity analyses.
RESULTS: Compared to no screening, the incremental cost-effectiveness ratio (ICER) was $16 166 per life year saved or $13 571 per QALY gained for the serology screening, and $38 792 per life year saved and $32 525 per QALY gained for the UBT. The ICER was $477 079 per life year saved or $390 337 per QALY gained for the UBT compared to the serology screening. The cost-effectiveness of serology screening over the UBT was robust to most parameters in the model.
CONCLUSION: The population-based serology screening for H pylori was more cost-effective than the UBT in prevention of gastric cancer in Singapore Chinese males.
doi:10.3748/wjg.14.3021
PMCID: PMC2712169  PMID: 18494053
Cost-effectiveness analysis; Gastric cancer; Helicobacter pylori; 13C-Urea breath test; Serology
6.  Is Chloroquine Better than Artemisinin Combination Therapy as First Line Treatment in Adult Nigerians with Uncomplicated Malaria?-A Cost Effectiveness Analysis 
The current case management and drug policy of malaria in Nigeria recommended by the Federal ministry of health may not be appropriate for all age categories. This suspicion was tested by running a cost effectiveness analysis of two possible and alternative strategies: Artemisinin Combination Therapy (ACT) or Chloroquine and ACT only if CQ fails (CANACT), in adult non pregnant Nigerians aged 20–45yrs. The result confirms that ACT is indeed more effective but also more costly with an incremental cost effectiveness ratio (ICER) of #2,546,527.00 per QALY that is much higher than the estimated upper limit of #25,000.00 that either patients or provider may be willing to pay. The CANACT strategy may be the most cost effective strategy in this subgroup of Nigerian patients and also provides better value for money.
PMCID: PMC3497851  PMID: 23878698
Malaria; Artemisinin Combination Therapy; Chloroquine; Incremental Cost effectiveness; Quality adjusted life years; Nigeria
7.  Cost-effectiveness of Tissue Plasminogen Activator in the 3 to 4.5 Hour Time-Window for Acute Ischemic Stroke 
Background
The aim of this study was to determine the cost-effectiveness of tPA treatment in the 3 to 4.5 hour time-window after ischemic stroke.
Methods
Decision-analytic and Markov state-transition models were created to determine the cost-effectiveness of treatment of ischemic stroke patients with intravenous tPA administered in the 3 to 4.5 hour time-window compared with medical therapy without tPA. Health benefits were measured in quality-adjusted life-years (QALYs). The economic outcome measure of the model was the difference in estimated healthcare costs between the two treatment alternatives. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the cost difference by the difference in QALYs. One-way sensitivity and probabilistic analyses were performed to test the robustness of the model.
Results
The administration of tPA over standard medical therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of $6,050, yielding an ICER of $21,978 per QALY. One-way sensitivity analyses demonstrated that the ICER was most sensitive to the cost of hospitalization for patients who received tPA. Based on probabilistic analysis there is 88% probability that tPA is the preferred treatment at a willingness to pay threshold of $50,000 per QALY.
Conclusion
The balance of costs and benefits favors treatment with intravenous tPA in the 3 to 4.5 hour time-window. This supports, from a societal perspective, the use of tPA therapy in this treatment time-window for acute ischemic stroke.
doi:10.1161/STROKEAHA.111.615682
PMCID: PMC3164239  PMID: 21719767
Stroke; tissue plasminogen activator; cost-effectiveness; quality-adjusted life-year
8.  Cost-effectiveness of early detection of breast cancer in Catalonia (Spain) 
BMC Cancer  2011;11:192.
Background
Breast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care.
Methods
We used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios.
Results
Strategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY.
Conclusions
A reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area.
doi:10.1186/1471-2407-11-192
PMCID: PMC3125279  PMID: 21605383
9.  Impact of Generic Alendronate Cost on the Cost-Effectiveness of Osteoporosis Screening and Treatment 
PLoS ONE  2012;7(3):e32879.
Introduction
Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women.
Methods
Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of “no screening” and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed.
Results
Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated.
Conclusions
Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less.
doi:10.1371/journal.pone.0032879
PMCID: PMC3302782  PMID: 22427903
10.  Association between body mass index and chronic kidney disease: A population-based, cross-sectional study of a Japanese community 
Chronic kidney disease (CKD) has recently been recognized as a risk factor for cardiovascular disease, while the mechanism by which CKD develops remained to be clarified. In the present study, we conducted a cross-sectional, community-based study to identify the factor(s) associated with CKD. We examined 1978 local residents of the Kiyotake area of Japan (697 males and 1281 females; age, 60.8 ± 11.0 years; mean ± SD), who had an annual health check-up. Diagnosis of CKD was made based on dipstick proteinuria of +1 or higher, or on a reduced glomerular filtration rate (GFR) estimated from serum creatinine level to less than 60 ml/min/1.73 m2. Body mass index (BMI) and prevalence of obesity in the residents with CKD were found to be higher than in those without CKD in both genders. When compared with the residents without CKD, the ratios of residents taking antihypertensive medicines were higher in both genders, and the blood pressure and fasting blood glucose levels of males and the triglyceride level of females were elevated in those with CKD. These parameters or factors were found to be significant for CKD by a univariate logistic analysis. We further analyzed the data with a multivariate logistic method using age, BMI, antihypertensive and antidyslipidemic medicines, blood pressure, serum lipid and glucose as independent covariates, and found that BMI was a significant parameter independently correlated with CKD in both genders. Thus, increased BMI is associated with CKD independently of blood pressure, serum lipid and glucose levels in the general population.
PMCID: PMC2672451  PMID: 19436662
chronic kidney disease; body mass index; general population
11.  Health economic assessment of ferric carboxymaltose in patients with iron deficiency and chronic heart failure based on the FAIR-HF trial: an analysis for the UK 
European Journal of Heart Failure  2012;14(7):782-790.
Aims
The purpose of this study was to evaluate the cost-effectiveness of iron repletion using intravenous (i.v.) ferric carboxymaltose (FCM) in chronic heart failure (CHF) patients with iron deficiency with or without anaemia. Cost-effectiveness was studied from the perspective of the National Health Service in the UK.
Methods and results
A model-based cost-effectiveness analysis was used to compare iron repletion with FCM with no iron treatment. Using data from the FAIR-HF trial and publicly available sources and publications, per patient costs and clinical effectiveness of FCM were estimated compared with placebo. Cost assessment was based on study drug and administration costs, cost of CHF treatment, and hospital length of stay. The incremental cost-effectiveness ratio (ICER) of FCM use was expressed as cost per quality-adjusted life year (QALY) gained, and sensitivity analyses were performed on the base case. The time horizon of the analysis was 24 weeks. Mean QALYs were higher in the FCM arm (difference 0.037 QALYs; bootstrap-based 95% confidence interval 0.017–0.060). The ICER of FCM compared with placebo was €4414 per QALY gained for the FAIR-HF dosing regimen. Sensitivity analyses confirmed the base case result to be robust.
Conclusion
From the UK payers’ perspective, managing iron deficiency in CHF patients using i.v. FCM was cost-effective in this analysis. The base case ICER was clearly below the threshold of €22 200–€33 300/QALY gained (£20 000–£30 000) typically used by the UK National Institute for Health and Clinical Excellence and proved to be robust in sensitivity analysis. Improved symptoms and better quality of life contributed to this result.
doi:10.1093/eurjhf/hfs083
PMCID: PMC3380546  PMID: 22689292
Chronic heart failure; Anaemia; Iron deficiency; Cost-effectiveness analysis; Healthcare costs
12.  Cost Effectiveness of Screening Strategies for Early Identification of HIV and HCV Infection in Injection Drug Users 
PLoS ONE  2012;7(9):e45176.
Objective
To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs) in opioid replacement therapy (ORT).
Design
Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15–59).
Methods
We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).
Results
Adding HIV and HCV viral RNA testing to antibody testing averts 14.8–30.3 HIV and 3.7–7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.
Discussion
Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3–6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.
doi:10.1371/journal.pone.0045176
PMCID: PMC3445468  PMID: 23028828
13.  The Cost-Effectiveness of Personalized Genetic Medicine 
Diabetes Care  2011;34(3):622-627.
OBJECTIVE
Neonatal diabetes mellitus is a rare form of diabetes diagnosed in infancy. Nearly half of patients with permanent neonatal diabetes have mutations in the genes for the ATP-sensitive potassium channel (KCNJ11 and ABCC8) that allow switching from insulin to sulfonylurea therapy. Although treatment conversion has dramatic benefits, the cost-effectiveness of routine genetic testing is unknown.
RESEARCH DESIGN AND METHODS
We conducted a societal cost-utility analysis comparing a policy of routine genetic testing to no testing among children with permanent neonatal diabetes. We used a simulation model of type 1 diabetic complications, with the outcome of interest being the incremental cost-effectiveness ratio (ICER, $/quality-adjusted life-year [QALY] gained) over 30 years of follow-up.
RESULTS
In the base case, the testing policy dominated the no-testing policy. The testing policy was projected to bring about quality-of-life benefits that enlarged over time (0.32 QALYs at 10 years, 0.70 at 30 years) and produced savings in total costs that were present as early as 10 years ($12,528 at 10 years, $30,437 at 30 years). Sensitivity analyses indicated that the testing policy would remain cost-saving as long as the prevalence of the genetic defects remained >3% and would retain an ICER <$200,000/QALY at prevalences between 0.7 and 3%.
CONCLUSIONS
Genetic testing in neonatal diabetes improves quality of life and lowers costs. This paradigmatic case study highlights the potential economic impact of applying the concepts of personalized genetic medicine to other disorders in the future.
doi:10.2337/dc10-1616
PMCID: PMC3041194  PMID: 21273495
14.  Residency Work-Hours Reform 
Background
In response to proposed federal legislation, the Accreditation Council for Graduate Medical Education limited resident work-hours in July 2003. The cost may be substantial but, if successful, the reform might lower preventable adverse event costs in hospital and after discharge.
Objectives
This study sought to estimate the reform's net cost in 2001 dollars, and to determine the reduction in preventable adverse events needed to make reform cost neutral from teaching hospital and societal perspectives.
Design
Cost analysis using published literature and data. Net costs were determined for 4 reform strategies and over a range of potential effects on preventable adverse events.
Results
Nationwide, transferring excess work to task-tailored substitutes (the lowest-level providers appropriate for noneducational tasks) would cost $673 million; mid-level providers would cost $1.1 billion. Reform strategies promoting adverse events would increase net teaching hospital and societal costs as well as mortality. If task-tailored substitutes decrease events by 5.1% or mid-level providers decrease them by 8.5%, reform would be cost neutral for society. Events must fall by 18.5% and 30.9%, respectively, to be cost neutral for teaching hospitals.
Conclusions
Because most preventable adverse event costs occur after discharge, a modest decline (5.1% to 8.5%) in them might make residency work-hours reform cost neutral for society but only a much larger drop (18.5% to 30.9%) would make it cost neutral for teaching hospitals, unless additional funds are allocated. Future research should evaluate which reform approaches prevent adverse events and at what cost.
doi:10.1111/j.1525-1497.2005.0133.x
PMCID: PMC1490222  PMID: 16191130
graduate medical education (GME); decision analysis; injury prevention; quality/performance improvement; accreditation; work-hours
15.  Cost-effectiveness of modified-release prednisone in the treatment of moderate to severe rheumatoid arthritis with morning stiffness based on directly elicited public preference values 
Background
Assessing the cost-effectiveness of treatments in rheumatoid arthritis (RA) is of growing importance due to the chronic nature of the disease, rising treatment costs, and budget-constrained health care systems. This analysis assesses the cost-effectiveness of modified-release (MR) prednisone compared with immediate-release (IR) prednisone for the treatment of morning stiffness due to RA.
Methods
A health state transition model was used to categorize RA patients into four health states, defined by duration of morning stiffness. The model applied a 1-year time horizon and adopted a UK National Health Service (NHS) perspective. Health benefits were measured in quality-adjusted life years (QALYs) and the final output was the incremental cost-effectiveness ratio (ICER). Efficacy data were derived from the CAPRA-1 (Circadian Administration of Prednisone in Rheumatoid Arthritis) study, drug costs from the British National Formulary (BNF), and utility data from a direct elicitation time-trade-off (TTO) study in the general population. Sensitivity analyses were conducted.
Results
Mean treatment costs per patient were higher for MR-prednisone (£649.70) than for IR-prednisone (£46.54) for the duration of the model. However, the model generated an incremental QALY of 0.044 in favor of MR-prednisone which resulted in an ICER of £13,577. Deterministic sensitivity analyses did not lead to significant changes in the ICER. Probabilistic sensitivity analysis reported that MR-prednisone had an 84% probability of being cost-effective at a willingness-to-pay threshold of £30,000 per QALY. The model only considers drug costs and there was a lack of comparative long-term data for IR-prednisone. Furthermore, utility benefits were not captured in the clinical setting.
Conclusion
This analysis demonstrates that, based on the CAPRA-1 trial and directly elicited public preference values, MR-prednisone is a cost-effective treatment option when compared with IR-prednisone for RA patients with morning stiffness over one year, according to commonly applied UK thresholds (£20,000–£30,000 per QALY). Further research into the costs of morning stiffness in RA is required.
doi:10.2147/CEOR.S47867
PMCID: PMC3816994  PMID: 24204166
modified-release prednisone; rheumatoid arthritis; morning stiffness; cost-effectiveness analysis; cost utility analysis; quality of life
16.  Economic Evaluation of Brief Psychodynamic Interpersonal Therapy in Patients with Multisomatoform Disorder 
PLoS ONE  2014;9(1):e83894.
Background
A brief psychodynamic interpersonal therapy (PIT) in patients with multisomatoform disorder has been recently shown to improve health-related quality of life.
Aims
To assess cost-effectiveness of PIT compared to enhanced medical care in patients with multisomatoform disorder.
Method
An economic evaluation alongside a randomised controlled trial (International Standard Randomised Controlled Trial Number ISRCTN23215121) conducted in 6 German academic outpatient centres was performed. Incremental cost-effectiveness ratio (ICER) was calculated from the statutory health insurance perspective on the basis of quality adjusted life years (QALYs) gained at 12 months. Uncertainty surrounding the cost-effectiveness of PIT was presented by means of a cost-effectiveness acceptability curve.
Results
Based on the complete-case analysis ICER was 41840 Euro per QALY. The results did not change greatly with the use of multiple imputation (ICER = 44222) and last observation carried forward (LOCF) approach to missing data (ICER = 46663). The probability of PIT being cost-effective exceeded 50% for thresholds of willingness to pay over 35 thousand Euros per QALY.
Conclusions
Cost-effectiveness of PIT is highly uncertain for thresholds of willingness to pay under 35 thousand Euros per QALY.
doi:10.1371/journal.pone.0083894
PMCID: PMC3898909  PMID: 24465387
17.  Cost Effectiveness Associated with Helicobacter pylori Screening and Eradication in Patients Taking Nonsteroidal Anti-Inflammatory Drugs and/or Aspirin 
Gut and Liver  2013;7(2):182-189.
Background/Aims
This study was performed to investigate the cost effectiveness of Helicobacter pylori screening/eradication in South Korean patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or aspirin.
Methods
A decision Markov model was used to estimate the effectiveness and economic impact of an H. pylori screening/eradication strategy compared to a no-screening strategy among patients who were included in the model at the age of 40 years. Utility weights were applied to four of the health status groups to reflect quality-adjusted life years (QALY). The costs of screening, H. pylori eradication, and managing peptic ulcer and ulcer complications were obtained from South Korea-specific data.
Results
The total costs per patient were US $2,454 for the H. pylori screening/eradication and US $3,182 for the no-screening strategy. The QALYs for the two strategies were 16.05 and 15.73, respectively. The results were robust for the analyses of all different cohort groups who entered the model at the age of 30, 50, or 60 years and for NSAIDs-naïve patients. Through the probabilistic sensitivity analysis, the robustness of our study's results was also determined.
Conclusions
The H. pylori screening/eradication strategy was found to be less expensive and more effective compared to the no-screening strategy among South Korean patients taking NSAIDs and/or aspirin.
doi:10.5009/gnl.2013.7.2.182
PMCID: PMC3607772  PMID: 23560154
Cost-benefit analysis; Helicobacter pylori; Mass screening
18.  Cost-effectiveness of Xpert® MTB/RIF for diagnosing pulmonary tuberculosis in the United States 
SUMMARY
SETTING
Conventional approaches to tuberculosis (TB) diagnosis and resistance testing are slow. The Xpert® MTB/RIF assay is an emerging molecular diagnostic assay for rapid TB diagnosis, offering results within 2 hours. However, the cost-effectiveness of implementing Xpert in settings with low TB prevalence, such as the United States, is unknown.
OBJECTIVE
We evaluated the cost-effectiveness of incorporating Xpert into TB diagnostic algorithms in the United States compared to existing diagnostics.
DESIGN
A decision-analysis model compared current TB diagnostic algorithms in the United States to algorithms incorporating Xpert. Primary outcomes were the costs and quality-adjusted life years (QALYs) accrued with each strategy; cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER).
RESULTS
Xpert testing of a single sputum sample from TB suspects is expected to result in lower total health care costs per patient (US$2673) compared to diagnostic algorithms using only sputum microscopy and culture (US$2728) and improved health outcomes (6.32 QALYs gained per 1000 TB suspects). Compared to existing molecular assays, implementation of Xpert in the United States would be considered highly cost-effective (ICER US$39 992 per QALY gained).
CONCLUSION
TB diagnostic algorithms incorporating Xpert in the United States are highly cost-effective.
doi:10.5588/ijtld.13.0095
PMCID: PMC3891798  PMID: 24025386
GeneXpert; MTD; diagnostics
19.  Influence of Patient Preferences on the Cost-Effectiveness of Screening for Lynch Syndrome 
Journal of Oncology Practice  2012;8(3 Suppl):e24s-e30s.
This cost-utility analysis reports on the effect of quality of life on the value of screening all new patients with colorectal cancer for Lynch syndrome.
Purpose:
Patients and relatives have varying preferences for genetic testing and interventions related to hereditary cancer syndromes. We examined how the impact of these services on quality of life (QoL) affects the cost-effectiveness of screening for Lynch syndrome among probands newly diagnosed with colorectal cancer and their relatives.
Methods:
We constructed a state-transition model comparing screening strategies (clinical criteria, prediction algorithms, tumor testing, and upfront germline testing) with no screening to identify Lynch syndrome. The model incorporated individuals' health state utilities after screening, germline testing, and risk-reducing surgeries, with utilities persisting for 12 months in the base case. Outcomes consisted of quality-adjusted life-years (QALYs), costs, and cost per QALY gained. Sensitivity analyses assessed how the duration and magnitude of changes in QoL influenced results.
Results:
Multiple screening strategies yielded gains in QALYs at acceptable costs compared with no screening. The preferred strategy—immunohistochemistry of tumors followed by BRAF mutation testing (IHC/BRAF)—cost $59,700 per QALY gained in the base case. The duration and magnitude of decreases in QoL after decisions related to germline testing and surgeries were key determinants of the cost-effectiveness of screening. IHC/BRAF cost > $100,000 per QALY gained when decrements to QoL persisted for 21 months.
Conclusion:
Screening for Lynch syndrome in the population is likely to yield long-term gains in life expectancy that outweigh any short-term decreases in QoL, at acceptable costs. Counseling for individuals should aim to mitigate potential negative impact of genetic testing and risk-reducing interventions on QoL.
doi:10.1200/JOP.2011.000535
PMCID: PMC3348599  PMID: 22942831
20.  Does Variation in Either Age at Start of Therapy or Duration of Therapy Make Chemoprevention with Finasteride Cost-Effective? 
Background
Incremental cost-effectiveness ratios (ICER) of finasteride for prostate cancer prevention are consistent with estimates beyond $100,000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50–55yrs. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride.
Methods
A probabilistic Markov model was designed to estimate lifetime prostate health related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared.
Results
The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88,800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142,300 per when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64,700 per QALY (base case 1) and $118,600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention.
Conclusion
Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100,000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug.
doi:10.1038/pcan.2012.26
PMCID: PMC3666586  PMID: 22777393
chemoprevention; prostate cancer; finasteride; cost-effectiveness analysis; age
21.  The economics of treating chronic hepatitis B in Asia 
Hepatology International  2008;2(3):284-295.
Chronic hepatitis B constitutes a significant health and economic burden to Asian countries. Six medications are now approved for the treatment of chronic hepatitis B, but there is still significant uncertainty with regards to treatment outcomes, cost impact, and benefits in view of the absence of long-term outcomes data. Cost-effectiveness Markov modeling thus allows us to project and estimate long-term outcomes based on current data and compare the cost–benefit between different treatment options. However, there are limitations to these reported studies. Cost-utility indices such as cost/quality–adjusted life years (cost/QALY) may not be intuitive to clinicians and patients. These studies are also usually based on first-world economies, using a benchmark of US$50,000/QALY, and cannot be extrapolated directly to Asia-Pacific countries. Cost-effectiveness of various treatment strategies using a combination of cost-effectiveness indices may provide a more complete picture. These include cost/HBeAg seroconversion for HBeAg-positive patients (range: US$19,400–30,800) and cost/HBV DNA negative (PCR assay) for HBeAg-negative patients (range: US$14,400–32,000) over 5-year time horizon; cost per cirrhosis prevented (range: US$326,000–686,000) and cost per HCC prevented (range: US$654,000–1,380,000) over 10-year horizon using data from REVEAL study, cost per end point complication prevented in cirrhotics (US$9,630/year), and cost per HCC prevented in cirrhotics (US$ 27,600/year) over a 32-month horizon, using data from Asia Lamivudine Cirrhosis Study. More potent antivirals with low resistance appear to have lower cost/clinical end point averted. Published reports of cost-utility analysis comparing treatment using conventional cost/QALY show that all treatment modalities fall below the first-world benchmark of US$50,000/QALY but vary in modeling assumptions and in quality, making comparisons difficult. Reimbursement policies affect out-of-pocket expenses to the patient, and increases the proportion of patients who can afford therapy, but generally do not affect cost-effectiveness. In conclusion, cost-effectiveness analysis is an important tool for health care administrators, clinicians, and patients to decide on the optimal therapy for chronic hepatitis B, but the methodology permits considerable leeway for interpretation of results, thus a combination of cost-effective indices may be needed to paint a more complete picture.
doi:10.1007/s12072-008-9049-2
PMCID: PMC2716880  PMID: 19669256
Hepatitis B treatment; Cost-effectiveness analysis
22.  The cost of schizophrenia in Japan 
Introduction:
Schizophrenia is a disorder that produces considerable burdens due to its often relapsing/remitting or chronic longitudinal course. This burden is felt not only by patients themselves, but also by their families and health care systems. Although the societal burden caused by this disorder has been evaluated in several countries, the magnitude of the societal cost of schizophrenia in Japan has never been estimated. The aim of this study is to clarify the societal burden of schizophrenia by estimating the cost of schizophrenia in Japan in 2008.
Methods:
A human capital approach was adopted to estimate the cost of schizophrenia. The total cost of schizophrenia was calculated as the sum of the direct, morbidity, and mortality costs. Schizophrenia was defined as disorders coded as F20.0–F20.9 according to the International Classification of Diseases-10. The data required to estimate the total cost was collected from publicly available statistics or previously reported studies.
Results:
The total cost of schizophrenia in Japan in 2008 was JPY 2.77 trillion (USD 23.8 billion). While the direct cost was JPY 0.770 trillion (USD 6.59 billion), the morbidity and mortality costs were JPY 1.85 trillion (USD 15.8 billion) and JPY 0.155 trillion (USD 1.33 billion), respectively.
Conclusion:
The societal burden caused by schizophrenia is tremendous in Japan, similar to that in other developed countries where published data exist. Compared with other disorders, such as depression or anxiety disorders, the direct cost accounted for a relatively high proportion of the total cost. Furthermore, absolute costs arising from unemployment were larger, while the prevalence rate was smaller, than the corresponding results for depression or anxiety in Japan.
doi:10.2147/NDT.S41632
PMCID: PMC3682806  PMID: 23785238
cost of illness; schizophrenia; societal burden; cost analysis; societal cost
23.  The cost-effectiveness of telestroke in the treatment of acute ischemic stroke 
Neurology  2011;77(17):1590-1598.
Objective:
To conduct a cost-effectiveness analysis of telestroke—a 2-way, audiovisual technology that links stroke specialists to remote emergency department physicians and their stroke patients—compared to usual care (i.e., remote emergency departments without telestroke consultation or stroke experts).
Methods:
A decision-analytic model was developed for both 90-day and lifetime horizons. Model inputs were taken from published literature where available and supplemented with western states' telestroke experiences. Costs were gathered using a societal perspective and converted to 2008 US dollars. Quality-adjusted life-years (QALYs) gained were combined with costs to generate incremental cost-effectiveness ratios (ICERs). In the lifetime horizon model, both costs and QALYs were discounted at 3% annually. Both one-way sensitivity analyses and Monte Carlo simulations were performed.
Results:
In the base case analysis, compared to usual care, telestroke results in an ICER of $108,363/QALY in the 90-day horizon and $2,449/QALY in the lifetime horizon. For the 90-day and lifetime horizons, 37.5% and 99.7% of 10,000 Monte Carlo simulations yielded ICERs <$50,000/QALY, a ratio commonly considered acceptable in the United States.
Conclusion:
When a lifetime perspective is taken, telestroke appears cost-effective compared to usual care, since telestroke costs are upfront but benefits of improved stroke care are lifelong. If barriers to use such as low reimbursement rates and high equipment costs are reduced, telestroke has the potential to diminish the striking geographic disparities of acute stroke care in the United States.
doi:10.1212/WNL.0b013e318234332d
PMCID: PMC3198982  PMID: 21917781
24.  Cost-effectiveness of treating resistant hypertension with an implantable carotid body stimulator 
Introduction
The purposes of this study are to investigate the cost-effectiveness of an implantable carotid body stimulator (Rheos®) for treating resistant hypertension and determine the range of starting systolic blood pressure (SBP) values where the device remains cost-effective.
Methods
A Markov model compared a 20 mmHg drop in SBP from an initial level of 180 with Rheos® to failed medical management in a hypothetical 50-year old cohort. Direct costs (2007$), utilities and event rates for future myocardial infarction, stroke, heart failure and end-stage renal disease were modeled. Sensitivity analyses tested the assumptions in the model.
Results
The incremental cost-effectiveness ratio (ICER) for Rheos® was $64,400 per quality-adjusted life-year (QALY) using Framingham-derived event probabilities. The ICER was <$100,000/QALY for SBPs ≥142. A probability of device removal of <1% per year or SBP reductions of ≥24 mmHg were variables that decreased the ICER below $50,000/QALY. For cohort characteristics similar to ASCOT-BPLA trial participants, the ICER became $26,700/QALY. Two-way sensitivity analyses demonstrated that lowering SBP 12 mmHg from 220 or 21 mmHg from 140 were required.
Conclusions
Rheos® may be cost-effective, with an ICER between $50,000-$100,000/QALY. Cohort characteristics and efficacy are key to the cost-effectiveness of new therapies for resistant hypertension.
doi:10.1111/j.1751-7176.2009.00163.x
PMCID: PMC3690459  PMID: 19817936
hypertension; blood pressure; cost-effectiveness; prosthesis and implants
25.  WTP for a QALY and health states: More money for severer health states? 
Background
In economic evaluation, cost per quality-adjusted life year (QALY) is generally used as an indicator for cost-effectiveness. Although JPY 5 million to 6 million (USD 60, 000 to 75,000) per QALY is frequently referred to as a threshold in Japan, do all QALYs have the same monetary value?
Methods
To examine the relationship between severity of health status and monetary value of a QALY, we obtained willingness to pay (WTP) values for one additional QALY in eight patterns of health states. We randomly sampled approximately 2,400 respondents from an online panel. To avoid misunderstanding, we randomly allocated respondents to one of 16 questionnaires, with 250 responses expected for each pattern. After respondents were asked whether they wanted to purchase the treatment, double-bounded dichotomous choice method was used to obtain WTP values.
Results
The results clearly show that the WTP per QALY is higher for worse health states than for better health states. The slope was about JPY −1 million per 0.1 utility score increase. The mean and median WTP values per QALY for 16 health states were JPY 5 million, consistent with our previous survey. For respondents who wanted to purchase the treatment, WTP values were significantly correlated with household income.
Conclusion
This survey shows that QALY based on the EQ-5D does not necessarily have the same monetary value. The WTP per QALY should range from JPY 2 million (USD 20,000) to JPY 8 million (USD 80,000), corresponding to the severity of health states.
doi:10.1186/1478-7547-11-22
PMCID: PMC3766196  PMID: 24128004
Quality-adjusted life years; Willingness-to-pay; Threshold; Cost-effectiveness analysis

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