Cost-effectiveness of left atrial appendage closure with Watchman for non-valvular atrial fibrillation patients in Japan.

AIMS: Left atrial appendage closure (LAAC) has been demonstrated to be cost-saving relative to oral anticoagulants for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) in the United States and Europe. This study assessed the cost-effectiveness of LAAC with the Watchman device relative to warfarin and direct oral anticoagulants (DOACs) for stroke risk reduction in NVAF from a Japanese public healthcare payer perspective. METHODS: A Markov model was developed with 70-year-old patients using a lifetime time horizon. LAAC clinical inputs were from pooled, 5-year PROTECT AF and PREVAIL trials; warfarin and DOAC inputs were from published meta-analyses. Baseline stroke and bleeding risks were from the SALUTE trial on LAAC. Cost inputs were from the Japanese Medical Data Vision database. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Over the lifetime time horizon, LAAC was less costly than warfarin (savings of JPY 1,878,335, equivalent to US $17,600) and DOACs (savings of JPY 1,198,096, equivalent to US $11,226). LAAC also provided 1.500 more incremental quality-adjusted life years (QALYs) than warfarin and 0.996 more than DOACs. In probabilistic sensitivity analysis, LAAC was cost-effective relative to warfarin and DOACs in 99.98% and 99.73% of simulations, respectively. LAAC dominated (had higher cumulative QALYs and was less costly than) warfarin and DOACs in 89.94% and 83.35% of simulations, respectively. CONCLUSIONS: Over a lifetime time horizon, LAAC is cost-saving relative to warfarin and DOACs for stroke risk reduction in NVAF patients in Japan and is associated with improved quality-of-life.

This study examined the cost-effectiveness of left atrial appendage closure (LAAC) compared to oral anticoagulants for stroke risk reduction among individuals with a specific type of irregular heart rhythm called non-valvular atrial fibrillation (NVAF). This study evaluated the cost-effectiveness of LAAC using the Watchman device in comparison to warfarin and direct oral anticoagulants (DOACs) from the perspective of Japan's public healthcare system. To investigate this, a computer-based model was developed involving 70-year-old patients over their lifetime. Data from notable studies such as the PROTECT AF and PREVAIL trials (covering 5 years) for LAAC and published meta-analyses for warfarin and DOACs were incorporated into the model. Baseline stroke and bleeding risks were derived from the SALUTE trial on LAAC. Cost inputs were based on data from the Japanese Medical Data Vision database. Additionally, we performed thorough cost-effectiveness analyses, including probabilistic and one-way sensitivity assessments. Our findings revealed that, over a lifetime, LAAC was more cost-effective than both warfarin and DOACs. Further, LAAC contributed an additional 1.500 quality-adjusted life years (QALYs) compared to warfarin and 0.996 QALYs compared to DOACs. In the long-term, adopting LAAC as an alternative to warfarin and DOACs is a cost-effective strategy for reducing stroke risk in NVAF patients in Japan. Moreover, it is associated with enhanced quality-of-life. These findings hold significant implications for informing decision-making in healthcare policies and clinical practices for NVAF patients.

A Theory of Diagnostic Testing to Stop the Virus Spreading: Evidence-based Reasoning to Resolve the COVID-19 Crisis by Testing.

In this study, the complicated reasoning and processes inherent in diagnostic testing were analyzed, and a mathematical theory was developed for effectively stopping the transmission of infection in the context of coronavirus disease 2019 (COVID-19). As a result of this work, a new formula was developed for the "boundary condition for contagion containment," which, based on a horizontal transmission model, gives the lower limit of sensitivity for a diagnostic test to stop the virus spreading. Two parameters are considered in the model: the level of transmission and the effective reproduction number. In example computations, the formula indicated that a one-off polymerase chain reaction-based test with a sensitivity of 85% would not be sufficient to contain highly contagious infections such as the Delta variant of SARS-CoV-2, which would likely require a sensitivity close to 100% for its containment. Furthermore, a cascade judgment system for multiple tests was proposed and examined as a form of triplet test system. This approach can enhance the accuracy of COVID-19 testing up to the minimum level needed to stop the virus spreading. The theory developed in this study will not only contribute as an academic exercise, but also be useful for making evidence-based decisions on public policy for pandemic control.

Cost-effectiveness analysis of branded and authorized generic celecoxib for patients with chronic pain in Japan.

OBJECTIVES: The aim of this study was to examine the cost-effectiveness of branded and authorized generic (AG) celecoxib for chronic pain patients with osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain (LBP), using real-world cost information for loxoprofen and pharmacotherapy for gastrointestinal bleeding. METHODS: This cost-effectiveness analysis was performed as a long-term simulation using the Markov model from the Japanese public healthcare payer's perspective. The analysis was conducted using loxoprofen with real-world weighted price by branded/generic distribution (hereinafter, loxoprofen with weighted price) as a comparator. In the model, we simulated the prognosis of patients with chronic pain by OA, RA, and LBP treated with loxoprofen or celecoxib, over a lifetime period. RESULTS: A cost-increase of 129,688 JPY (1,245.00 USD) for branded celecoxib and a cost-reduction of 6,268 JPY (60.17 USD) for AG celecoxib were recognized per patient in lifetime horizon, compared to loxoprofen with weighted price. No case was recognized to reverse the results of cost-saving by AG celecoxib in one-way sensitivity analysis. The incremental cost-effectiveness ratio of branded celecoxib attained 5,403,667 JPY/QALY (51,875.20 USD/QALY), compared to loxoprofen with the weighted price. CONCLUSION: The current cost-effectiveness analysis for AG celecoxib revealed its good value for costs, considering the patients' future risk of gastrointestinal injury; also, the impact on costs due to AG celecoxib against loxoprofen will be small. It implies that the disadvantage of AG celecoxib being slightly more expensive than generic loxoprofen could be offset by the good cost-effectiveness during the prognosis.

Efficacy of biologic therapies for biologic-naïve Japanese patients with moderately to severely active ulcerative colitis: a network meta-analysis.

BACKGROUND/AIMS: Several biologic therapies are approved in Japan to treat moderately to severely active ulcerative colitis (UC), but there are no published comparative efficacy studies in a Japanese population. We compared the efficacy of biologics approved in Japan (adalimumab, infliximab, golimumab, and vedolizumab) for treating biologic-naïve patients with UC at their approved doses. METHODS: A targeted literature review identified 4 randomized controlled trials of biologics for UC in biologicnaïve Japanese patients. For each study, efficacy outcome data from induction (weeks 6-12) and maintenance (weeks 30-60) treatment were extracted for analysis. Treatment effects on clinical response, clinical remission, and mucosal healing relative to the average placebo results across all trials were estimated using network meta-analyses followed by transformation into probabilities and odds ratios (OR). RESULTS: At the end of induction, the likelihood of clinical response and clinical remission was highest with infliximab (OR: 2.12 and 2.35, respectively) and vedolizumab (OR: 2.10 and 2.32, respectively); the likelihood of mucosal healing was highest with infliximab (OR: 2.24) and adalimumab (OR: 1.86). During maintenance, the likelihood of clinical response and clinical remission was highest with vedolizumab (OR: 6.44 and 4.68, respectively) and golimumab (OR: 5.13 and 3.84, respectively); the likelihood of mucosal healing was significantly higher than placebo with all biologics. CONCLUSIONS: All active treatments were efficacious compared with placebo. Infliximab and vedolizumab had the highest odds for induction of clinical response, remission, and mucosal healing. Golimumab and vedolizumab had numerically higher odds of achieving efficacy outcomes in the maintenance phase.

Health technology assessment in Japan: a work in progress.

Background: In Japan, pharmacoeconomic requirements for list-price adjustment were institutionalized in April 2019 following provisional implementation of a new Health Technology Assessment (HTA) program 2016-2019. Since April 2019, submission of cost-effectiveness evidence to the Central Social Insurance Medical Council (Chuikyo) as part of the Japanese Ministry of Health, Labour, and Welfare has been mandatory for selected pharmaceuticals and medical devices.Methods: Based on a review of publications and commentaries since April 2019, together with views from a group of experts on key issues to be addressed, this report provides an update on recent HTA developments and key challenges still to be addressed.Results and Discussion: Japan's new HTA program is a first step toward development of a universal healthcare system that can be sustainable for many years into the future. Currently, Japan's HTA program requires provision of incremental cost-effectiveness ratios (ICERs) as evidence, with quality-adjusted life years as the preferred outcome measure. Prices can be adjusted both upward and downward according to the degree of the ICER estimate. Japan is the first country to have adopted an algorithmic method for "ICER-based" pricing; however, HTA measures that extend beyond a single ICER estimate are needed to take full advantage of HTA in the future. In particular, generation of evidence of value should support changes to the healthcare system so that incentives for innovation are not diminished while industry and government are not overburdened by the generation or assessment of evidence. There is a need to ensure scientifically sound HTA expertise across all sectors in Japan, and therefore enhancement of HTA literacy and capability among healthcare professionals, academia, government, and industry should be a priority.

The Development of Health Technology Assessment in Asia: Current Status and Future Trends.

Health technology assessment (HTA) has long been employed by many countries around the world, but its adoption in Asia has been slower. Only recently have a growing number of Asian countries started to implement HTA for pricing and reimbursement decisions. The objective of this article is to provide an overview of how HTA has been or is being implemented in Asia within the context of a country's existing-and often complex-coverage, reimbursement, and pricing schemes. Three countries at different stages of HTA implementation were selected as case studies: South Korea, where there is a young yet established HTA program; Japan, where a 3-year HTA pilot program has just concluded; and China, where HTA efforts are underway but have not been formally implemented. Not only do the experiences of these 3 countries well exemplify how the organization and scope of HTA can be customized to meet a country's unique healthcare needs, but they also provide the opportunity to outline some common key challenges that must be overcome to implement and develop HTA competencies and capabilities.

Pharmaceutical pricing in Japan: market evidence for rheumatoid arthritis treatment.

BACKGROUND: Drug price setting is one of the key challenges faced by the Japanese health care system. This study aims to identify the determinants of drug price in Japan using the example of the rheumatoid arthritis (RA) treatment market. RESEARCH DESIGN AND METHODS: In order to compare prices across different products, we calculated prices per defined daily dose using WHO methodology. Price determinants were calculated both at launch and over time using IMS quarterly data on medicines approved for RA treatment in Japan from 2012 to 2015. Pharmaceutical pricing was modeled as a function of clinical and economic variables using regression analysis. RESULTS: For prices at the launch we found that differences in efficacy are not reflected in price differentials. We also report that the number of products within a molecule class had a negative effect on prices while originator drugs maintained higher prices. CONCLUSION: Although the existing pricing rules in Japan are very comprehensive they do not necessarily capture differences in product characteristics. The findings here support the notion that competitive forces are weak in highly regulated markets such as Japan.

A NEW HEALTH TECHNOLOGY ASSESSMENT SYSTEM FOR JAPAN? SIMULATING THE POTENTIAL IMPACT ON THE PRICE OF SIMEPREVIR.

OBJECTIVES: Japanese authorities have announced a plan to introduce a health technology assessment (HTA) system in 2016. This study assessed the potential impact of such a policy on the price of the antivirologic drug simeprevir. METHODS: Taking the antivirologic drug simeprevir as an example, we compared the current Japanese price with hypothetical prices that might result if a U.K. (cost-utility) or German (efficiency frontier) style HTA assessment was in place. RESULTS: The simeprevir unit price under the current Japanese pricing scheme is 13,122 Japanese yen (equivalent to 109.35 U.S. dollars as of April 2015). Depending on the selection of comparators and the pricing method, and assuming that HTA will be used as a basis for price setting, the estimated prices of simeprevir vary up to four times higher than under the current Japanese pricing scheme. CONCLUSIONS: Although the analysis is based on only one drug, it cannot be taken for granted that a new HTA system would reduce public healthcare expenditure in Japan.

Determinants of Glycated Hemoglobin in Subjects With Impaired Glucose Tolerance: Subanalysis of the Japan Diabetes Prevention Program.

BACKGROUND: Limited evidence is available about the relationship of lifestyle factors with glycated hemoglobin (HbA1c) in subjects with impaired glucose tolerance. The aim of study was to identify such determinant factors of HbA1c in subjects with impaired glucose tolerance. METHODS: This cross-sectional study included 121 men and 124 women with impaired glucose tolerance, who were diagnosed based on a 75-g oral glucose tolerance test. Demographic and biochemical parameters, including the body mass index (BMI), fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and HbA1c, were measured. The pancreatic ß-cell function and insulin resistance were assessed using homeostasis model assessment (HOMA-ß). Dietary intake was assessed by a food frequency questionnaire. RESULTS: The levels of FPG, 2-h PG, and carbohydrate intake were correlated with the HbA1c level in men, while the FPG and 2-h PG levels were correlated with the HbA1c level in women. In multiple regression analyses, BMI, FPG, 2-h PG, and white rice intake were associated with HbA1c levels in men, while BMI, FPG, HOMA-ß, and bread intake were associated with HbA1c levels in women. CONCLUSIONS: The present findings suggest that a substantial portion of HbA1c may be composed of not only glycemic but also several lifestyle factors in men with impaired glucose tolerance. These factors can be taken into consideration as modifiable determinants in assessing the HbA1c level for the diagnosis and therapeutic monitoring of the disease course.

Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to beta-3 adrenergic receptor gene polymorphism Trp64Arg(C/T): Results from the Japan Diabetes Prevention Program.

The beta-3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance. Data were analyzed from 112 patients with impaired glucose tolerance in the Japan Diabetes Prevention Program, a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group or usual care group. Changes in weight and metabolic parameters were measured after the 6-month intervention. The ADRB3 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. Non-carriers showed a greater weight reduction compared with the carriers in both the lifestyle intervention group and usual care group, and a greater increase of high-density lipoprotein cholesterol levels than the carriers only in the lifestyle intervention group. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance patients.

Estimating the cost-effectiveness of daclatasvir plus asunaprevir in difficult to treat Japanese patients chronically infected with hepatitis C genotype 1b.

AIM: Standard of care for chronic hepatitis C in Japan is currently a pegylated interferon (IFN)-α + ribavirin (PR)-based regimen, notably associated with efficacy and tolerability issues. The advent of novel direct-acting antivirals (DAA) has provided more efficacious and better tolerated treatments. This study investigated the cost-effectiveness of the daclatasvir + asunaprevir (DCV + ASV) DAA regimen in patients infected with hepatitis C virus (HCV) genotype 1b who had previously not responded to or were ineligible for IFN-containing regimens. METHODS: A cost-utility analysis using an established Markov model compared DCV + ASV with simeprevir + PR (SMV + PR), telaprevir + PR (TVR + PR) and no treatment using Japanese-specific model inputs, with costs and utility values discounted at 2%. A cohort of patients was simulated until death and predicted quality-adjusted life-years (QALY) and costs were estimated. A subgroup analysis of patients with no DCV resistance was conducted. RESULTS: In all scenarios, DCV + ASV was predicted to be dominant over the comparator; namely, DCV + ASV was associated with increased QALY gains and decreased cost. In patients treated during the chronic hepatitis C stage, cost reductions were ¥1 057 288-2 619 206, and in patients treated during the compensated cirrhosis (CC) stage, reductions were ¥1 032 224-2 531 930. QALY gains were 0.749-2.609 and 0.874-3.043, respectively. Results improved when considering the subgroup of patients without DCV resistance. CONCLUSION: Cost-effectiveness conclusions are similar for patients treated in the chronic hepatitis C and CC disease stages, with DCV + ASV expected to be cost-saving versus standard of care in Japan for patients with HCV genotype 1b patients who have failed prior therapy or are IFN-ineligible/intolerant.

Healthcare Databases in Thailand and Japan: Potential Sources for Health Technology Assessment Research.

BACKGROUND: Health technology assessment (HTA) has been continuously used for value-based healthcare decisions over the last decade. Healthcare databases represent an important source of information for HTA, which has seen a surge in use in Western countries. Although HTA agencies have been established in Asia-Pacific region, application and understanding of healthcare databases for HTA is rather limited. Thus, we reviewed existing databases to assess their potential for HTA in Thailand where HTA has been used officially and Japan where HTA is going to be officially introduced. METHOD: Existing healthcare databases in Thailand and Japan were compiled and reviewed. Databases' characteristics e.g. name of database, host, scope/objective, time/sample size, design, data collection method, population/sample, and variables were described. Databases were assessed for its potential HTA use in terms of safety/efficacy/effectiveness, social/ethical, organization/professional, economic, and epidemiological domains. Request route for each database was also provided. RESULTS: Forty databases- 20 from Thailand and 20 from Japan-were included. These comprised of national censuses, surveys, registries, administrative data, and claimed databases. All databases were potentially used for epidemiological studies. In addition, data on mortality, morbidity, disability, adverse events, quality of life, service/technology utilization, length of stay, and economics were also found in some databases. However, access to patient-level data was limited since information about the databases was not available on public sources. CONCLUSION: Our findings have shown that existing databases provided valuable information for HTA research with limitation on accessibility. Mutual dialogue on healthcare database development and usage for HTA among Asia-Pacific region is needed.

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. METHODS: A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. FINDINGS: Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US $1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US $22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US $67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. CONCLUSION: Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF.

The augmented representation of the cost-effectiveness acceptability curve for economic evaluation of health technology.

New schemes on the cost-effectiveness acceptability curve (CEAC) were developed, which can make the CEAC augmented to be more informative regarding the types of acceptance and statistical inference. Theoretical approaches have been undertaken to address two questions: 1) how the area under the curve (AUC) can be zoned by different types of acceptance displayed on the incremental cost-effectiveness plane, and 2) how the accepted dataset of incremental cost-effectiveness ratios (ICERs), which are generated by simulation runs, can be statistically associated with a threshold of ICER for acceptance. To address the first question, the AUC of a typically sigmoid-shaped CEAC was divided into three zones according to the three segmentations of the scattered plots accepted at South-east, North-east and South-west quadrants on the incremental cost-effectiveness plane. A solution for the second question was "a new CEAC of the mean" (mCEAC), which is defined by plotting a pair of the mean and its occurrence probability of ICER accepted at North-east quadrant on the incremental cost-effectiveness plane. All those schemes were graphically illustrated based on hypothetical examples using the bootstrapping simulation. Our new schemes on CEAC will provide decision makers with useful information on cost-effectiveness assessment beyond the standard presentation of CEAC.

Effect of baseline HbA1c level on the development of diabetes by lifestyle intervention in primary healthcare settings: insights from subanalysis of the Japan Diabetes Prevention Program.

OBJECTIVES: To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. DESIGN: Randomized controlled trial. SETTING: 32 healthcare centers in Japan. PARTICIPANTS: Participants with IGT, aged 30-60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). INTERVENTIONS: During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. OUTCOME MEASURES: The primary endpoint was the development of T2DM based on an oral glucose tolerance test. RESULTS: The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels <5.7%. CONCLUSIONS: Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels <5.7%. TRIAL REGISTRATION NUMBER: UMIN000003136.

Regression analysis of indicating multiple incremental cost-effectiveness ratios for non-small cell lung cancer treatment.

OBJECTIVES: The value of a health technology can be measured in terms of cost and benefit on two-dimensional co-ordinates. This study is to quantitatively analyze the correlation and to conduct a regression on the X-Y plane constituted by cost and QALYs (quality-adjusted life years) associated with the first line treatment, the maintenance treatment, and the second line treatment for non-small cell lung cancer (NSCLC). METHODS: The cost-effectiveness data of the cost and QALYs were extracted, with respect to the three categories of the NSCLC treatment, from the CEA Registry at Tufts Medical Center, regarding the literature published from 2000-2011. As a result, 44 QALY-cost ratios were identified. RESULTS: Based on those extracted data, the correlation and regression analyses were performed by mathematical model using log and square-root functions. The plotted ratios stratified by the three stages for the NSCLC treatment were visually grouped into three clusters. There were statistically significant differences among the correlation coefficients of the cluster. In regression, the log model was found to be better fitted than the square-root model; formulating QALY = -1.12 + 0.16 log(Cost), -1.99 + 0.28 log(Cost), and -0.69 + 0.10 log(Cost) for the first line, the maintenance, and the second line treatment, respectively. Monetary units were standardized to 2008 US dollars. CONCLUSION: A good methodological potential was confirmed so as to assess the Incremental Cost Effectiveness Ratio (ICER) variations, considering stratification by multiple factors such as disease and treatment categories. This study has certain limitations, such as the small number of included articles and the stratification, not reflecting a factor of new genetic findings.

Multicountry burden of chronic hepatitis C viral infection among those aware of their diagnosis: a patient survey.

BACKGROUND: The World Health Organization has called for global and regional assessments of the burden of hepatitis C (HCV) along with country-specific patient profiles to better inform healthcare policy. The present investigated the characteristics and burden of patients reporting a diagnosis of HCV infection in the US, France, Germany, Italy, Spain, the UK, urban China, and Japan using a consistent methodology of patient-reported surveys. METHODS: The 2010 5EU (N = 57,805), 2009 US (N = 75,000), 2008/2009 Japan (N = 37,683), and 2009/2010 urban China (N = 33,261) waves of the National Health and Wellness Survey were used as the data source. Within each country, patients with a self-reported diagnosis of HCV were compared with those who did not report a diagnosis of HCV on sociodemographics, health behaviors, comorbidities, and health outcomes (e.g., Short Form-12v2). The effect of HCV was examined using regression analysis applying sampling weights. RESULTS: The prevalence of HCV ranged from 0.26% (China) to 1.42% (Italy). Patients in Japan and Italy (61.60 and 61.02 years, respectively) were the oldest, while patients in the US were the most likely to be obese (39.31%) and have concomitant anxiety (38.43%) and depression (46.05%) compared with other countries. Pooling countries and adjusting for sociodemographics, health behaviors, and comorbidities, HCV was associated with significantly lower physical component summary scores (b = -2.51) and health utilities (b = -0.04) and greater overall work impairment (b = 8.79), physician visits (b = 2.91), and emergency department visits (b = 0.30) (all p<.05). The effects on health status were strongest in the US and UK while the effects on healthcare resource use were strongest in Japan. CONCLUSIONS: HCV was associated with a significant humanistic and economic burden. These results suggest that the manifestation of the HCV burden, and the profile of the patients themselves, varied dramatically by country. Successful disease management should be cognizant of region-specific unmet needs.

Estimating the Long-Term Clinical and Economic Outcomes of Daclatasvir Plus Asunaprevir in Difficult-to-Treat Japanese Patients Chronically Infected with Hepatitis C Genotype 1b.

OBJECTIVES: Japan has one of the highest endemic rates of hepatitis C virus (HCV) infection. Treatments in Japan are currently limited to interferon-alfa-based regimens, which are associated with tolerability and efficacy issues. A novel regimen combining two oral HCV therapies, daclatasvir and asunaprevir (DCV + ASV), has shown favorable results in Japanese patients with chronic genotype 1b HCV infection. Comparisons of clinical and economic outcomes associated with DCV + ASV treatment and current standards of care were investigated. METHODS: The MOdelling the NAtural histoRy and Cost-effectiveness of Hepatitis cost-effectiveness model projected outcomes in 1000 patients aged 70 years with either chronic hepatitis C or compensated cirrhosis over a lifetime simulation. Japanese-specific disease transition rates were used, and discounting was applied annually at a rate of 2%. Efficacy data for DCV + ASV and telaprevir triple therapy (telaprevir + pegylated interferon-alfa + ribavirin [TVR + pegIFN-α/RBV]) were obtained from a Japanese subgroup analysis found within a global meta-analysis: sustained virological response rates of 74%, 85%, and 87% were reported for null responders (NRs), partial responders (PRs), and interferon-alfa-ineligible/intolerant patients, respectively, treated with DCV + ASV, and rates of 42% and 59% were reported for NRs and PRs, respectively, treated with TVR + pegIFN-α/RBV. RESULTS: Initiating DCV + ASV treatment in patients in the chronic hepatitis C disease stage resulted in quality-adjusted life-year gains of 0.96 and 0.77 over TVR + pegIFN-α/RBV for NRs and PRs, respectively, and a gain of 2.61 in interferon-alfa-ineligible/intolerant patients over no treatment. Similarly, quality-adjusted life-year gains of 1.11, 0.90, and 3.05 were observed when initiating treatment in patients in the compensated cirrhosis stage. Cumulative lifetime events of decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality were reduced by up to 66, 115, and 128, respectively, with DCV + ASV treatment. CONCLUSIONS: There is a lack of successful therapies for patients with HCV who have previously failed to achieve sustained virological response or are ineligible for interferon-alfa-based therapies. Results demonstrate that the provision of an alternative, interferon-alfa-free regimen, such as DCV + ASV, offers significant value in terms of avoiding life-threatening liver complications and increasing patients' quality of life.

A warning index used in prescreening for Alzheimer's disease, based on self-reported cognitive deficits and vascular risk factors for dementia in elderly patients with type 2 diabetes.

Background/Aims. Diabetes might increase the risk of Alzheimer's disease (AD). For detecting dementia, it is typical to obtain informants' perceptions of cognitive deficits, but such interviews are usually difficult in routine care. We aimed to develop a model for predicting mild to moderate AD using a self-reported questionnaire and by evaluating vascular risk factors for dementia in elderly subjects with diabetes. Methods. We recruited 286 diabetic and 155 nondiabetic elderly subjects. There were 25 patients with AD and 261 cognitively normal individuals versus 30 with AD and 125 normal subjects, respectively. Each participant answered subjective questions on memory deficits and daily functioning. Information on vascular risk factors was obtained from clinical charts, and multivariate logistic regression was used to develop a model for predicting AD. Results. The predicted probabilities used in screening for AD in diabetic subjects constituted age, education, lower diastolic blood pressure, subjective complaints of memory dysfunction noticeable by others, and impaired medication, shopping, and travel outside a familiar locality. Receiver operating characteristic analysis revealed a satisfactory discrimination for AD specific for diabetic elderly subjects, with 95.2% sensitivity and 90.6% specificity. Conclusion. This is the first useful index that can prescreen for AD in elderly subjects with diabetes.