A Cross-Sectional Study Based on Forty Systematic Reviews of Foods with Function Claims (FFC) in Japan: Quality Assessment Using AMSTAR 2.

BACKGROUND: The Foods with Function Claims (FFC) was introduced in Japan in April 2015 to make more products available that are labeled with health functions. The products' functionality of function claims must be explained by scientific evidence presented in systematic reviews (SRs), but the quality of recent SRs is unclear. This study assessed the quality of SRs in the FFC registered on the Consumer Affairs Agency (CAA) website in Japan. METHODS: We searched the database from 1 April to 31 October 2022. Confidence in the methodological quality of each SR was evaluated by the AMSTAR 2 checklist. RESULTS: Forty SRs were randomly extracted on the basis of the eligibility criteria and recruitment procedures. Overall confidence was rated as "high" (N = 0, 0%), "moderate" (N = 0, 0%), "low" (N = 2, 5%), or "critically low" (N = 38, 95%). The mean AMSTAR 2 score was 51.1% (SD 12.1%; range 19-73%). Among the 40 SRs, the number of critical domain deficiencies was 4 in 7.5% of SRs, 3 in 52.5% of SRs, 2 in 35% of SRs, and 1 in 5% of SRs. Registering the review's protocol and comprehensive search strategies were particularly common deficiencies. Additionally, the risk of bias (RoB) was insufficiently considered. CONCLUSION: Overall, the methodological quality of the SRs based on the FFC, introduced eight years earlier, was very poor. This was especially true in the interpretation and discussion of critical domains, which had many deficiencies in terms of protocol registration, a comprehensive literature search strategy, and accounting for the RoB.

Budget impact analysis of comprehensive genomic profiling for untreated advanced or recurrent solid cancers in Japan.

AIMS: In Japan, the use of comprehensive genomic profiling (CGP) is only available for cancer patients who have no standard of care (SoC), or those who have completed SoC. This may lead to missed treatment opportunities for patients with druggable alterations. In this study, we evaluated the potential impact of CGP testing before SoC on medical costs and clinical outcome in untreated patients with advanced or recurrent biliary tract cancer (BTC), non-squamous non-small cell lung cancer (NSQ-NSCLC), or colorectal cancer (CRC) in Japan between 2022 and 2026. MATERIALS AND METHODS: We constructed a decision-tree model reflecting the healthcare environment of Japan, to estimate the clinical outcome and medical costs impact of CGP testing by comparing two groups (with vs without CGP testing before SoC). The epidemiological parameters, detection rates of druggable alterations, and overall survival were collected from literature and claims databases in Japan. Treatment options selected based on druggable alterations were set in the model based on clinical experts' opinions. RESULTS: In 2026, the number of untreated patients with advanced or recurrent BTC, NSQ-NSCLC, and CRC was estimated to be 8600, 32,103, and 24,896, respectively. Compared with the group without CGP testing before SoC, CGP testing before SoC increased druggable alteration detection and treatment rate with matched therapies in all three cancer types. The medical costs per patient per month were estimated to increase with CGP testing before SoC in the three cancer types by 19,600, 2900, and 2200 JPY (145, 21, and 16 USD), respectively. LIMITATIONS: Only those druggable alterations with matched therapies were considered in the analysis model, while the potential impact of other genomic alterations provided by CGP testing was not considered. CONCLUSIONS: The present study suggested that CGP testing before SoC may improve patient outcomes in various cancer types with a limited and controllable increase in medical costs.

An assessment of the use of complementary and alternative medicine by Korean people using an adapted version of the standardized international questionnaire (I-CAM-QK): a cross-sectional study of an internet survey.

BACKGROUND: In Korea, there are two types of medical doctors: one practises conventional medicine (hereafter called a physician), and the other practises traditional medicine (hereafter called a Korean medical doctor). This study aimed to compare the provision of complementary and alternative medicine (CAM) by these providers to CAM use per self-judgement in Korea. METHODS: We analysed 1668 Korean people via an internet survey with the Korean adopted version of the I-CAM-Q, namely, the International Questionnaire to measure use of CAM, to understand whether respondents used CAM based either on a prescription or advice from a physician or a Korean medical doctor or on self-judgement. RESULTS: In the previous 12 months, the proportions of respondents who were treated by a physician, who were treated by a Korean medical doctor and who were not treated by anyone were 67.9, 20.7 and 14.2%, respectively. Among the respondents who received CAM based on a prescription or advice from a physician, traditional Korean medicine practices and dietary supplements were commonly used; only a small percentage used other CAM therapies. Respondents who received CAM based on a prescription or advice from a Korean medical doctor showed similar results. Acupuncture and moxibustion, traditional Korean medicines (decoction), or cupping were more commonly used. Korean traditional medicines as over-the-counter (OTC) drugs were more commonly used by respondents who received CAM therapy based on a prescription or advice from a physician than by those who received CAM therapy based on a prescription or advice from a Korean medical doctor. A total of 74% of the responders used any CAM by self-judgement in the previous 12 months. CONCLUSIONS: For the use of CAM in Korea, in addition to the Korean traditional medical care provided by Korean medical doctors, general physicians advised people regarding Korean traditional medical care and dietary supplements.

Cost-utility analysis of sofosbuvir for the treatment of genotype 2 chronic hepatitis C in Japan.

OBJECTIVE: Across Japan, around 2 million people are infected with hepatitis C virus (HCV) with long-term complications such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplant (LT). Current treatment options have several limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological responses (SVR) rates, especially for the most severe patients. Sofosbuvir (SOF) is the first nucleotide analog NS5B polymerase inhibitor with pan-genotypic activity. SOF, administered in combination with ribavirin (RBV) with or without pegylated interferon (PEGIFN) resulted in high SVR rates across genotype (GT) 1-6 patients. It is also the first available regimen for patients that are unsuitable for interferon. This analysis assessed the cost-utility ratio of sofosbuvir in GT2 patients in Japan. RESEARCH DESIGN AND METHODS: A Markov model followed a cohort of 10,000 GT2 patients until patients reached 100 years of age. Approximately 20% of patients initiated treatment at the cirrhotic stage. Comparators were based on the current recommendations in Japan, including PEGIFN with ribavirin (RBV), telaprevir (TVR) in combination with PEGIFN + RBV and no treatment. Costs and outcomes were discounted at 2%. RESULTS: Sofosbuvir was cost-effective across all the studied indications, especially in patients unsuitable for interferon, with incremental cost-effectiveness ratios (ICERs) lower than JPY 5,000,000. Compared to the other treatments included in the analysis, SOF + RBV resulted in improved clinical outcomes. Results were robust to sensitivity analyses. CONCLUSION: SOF combined with RBV was shown to be cost-effective in GT2 patients in Japan. Compared to PEGIFN + RBV, TVR + PEGIFN + RBV and no treatment SOF offers a more efficacious, shorter and better tolerated treatment option and extends treatment to reach HCV-infected patients who are ineligible for interferon-based regimens. Although adverse events were not included in the analyses, this would not make any changes to our conclusion.

Quality of life assessment in cosmetics: specificity and interest of the international BeautyQol instrument.

The wide use of cosmetics and their perceived benefits upon well-being imply objective descriptions of their effects upon the different dimensions contributing to the quality of life (QoL). Such a goal pleas for using relevant and validated scientific instruments with robust measurement methods. This paper discusses the interest of the new validated questionnaire BeautyQoL specifically designed to assess the effect of cosmetic products on physical appearance and QoL. After conducting a review of skin appearance and QoL, three phases of the international codevelopment have been carried out in the following sequence: semi-directed interviews (Phase 1), acceptability study (Phase 2), and validation study (Phase 3). Data collection and validation process have been carried out in 16 languages. This review confirms that QoL instruments developed in dermatology are not suitable to assess cosmetic products, mainly because of their lack of sensitivity. General acceptability of BeautyQol was very good. Forty-two questions have been structured in five dimensions that explained 76.7% of the total variance: Social Life, Self-confidence, Mood, Vitality, and Attractiveness. Cronbach's alpha coefficients are between 0.932 and 0.978, confirming the good internal consistency of the results. The BeautyQol questionnaire is the first international instrument specific to cosmetic products and physical appearance that has been validated in 16 languages and could be used in a number of clinical trials and descriptive studies to demonstrate the added value of these products on the QoL.

Cost-minimization analysis of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency.

PURPOSE: IgPro20, Hizentra(®) an L-proline-stabilized 20% human subcutaneous immunoglobulin (SCIG), has been shown in a Phase III pivotal study to be well tolerated and efficacious in adult and pediatric Japanese patients with primary immunodeficiency. Economic aspects of SCIG treatment in comparison with previous intravenous immunoglobulin (IVIG) therapy were analyzed in this Phase III study in Japan. METHODS: Twenty-four Japanese patients with primary immunodeficiency on IVIG treatment were switched to IgPro20 at an equivalent dose (full analysis set). The study consisted of a screening period, an IVIG treatment period with 3 planned infusions every 3 or 4 weeks, a 12-week SCIG wash-in and wash-out period, and a 12-week SCIG efficacy period. The difference in medical cost and productivity loss resulting from changes in hospital frequency between the SCIG and IVIG treatment was evaluated. Information about treatment cost was collected as part of the Life Quality Index questionnaire. In addition, productivity loss and hospital-related absenteeism were evaluated. FINDINGS: Life Quality Index scores for all domains were higher with SCIG than with IVIG in this patient population. In the full analysis set, the mean (SD) Life Quality Index score of the Costs domain increased from 45.1 (26.34) at Week 1 (IVIG period) to 71.9 (18.52) at Week 24 (end of the SCIG efficacy period), representing a mean change of 26.74 and a large score improvement effect size (1.01). Median productivity loss was reduced by 60% from baseline to Weeks 12 and 24. This resulted in a reduction in costs of JPY 10,875 per patient per month at Weeks 12 and 24. Subcutaneous treatment with IgPro20 also reduced hospital-related absenteeism. The number of patients, parents, or guardians who were not absent from work or housework duties and had no reduction in working time increased from 4 (17.4%) at Week 1 to 9 (39.1%) at Week 24. Similar results were obtained in the per-protocol set (n = 21). IMPLICATIONS: Switching from IVIG to SCIG reduced markedly productivity loss and hospital-related absenteeism. The reduction in hospital visit frequency due to the use of home-based IgG therapy enabled by the change in administration route is expected to produce an important pharmacoeconomic benefit in Japan. Study Code: ZLB06_002CR, ClinicalTrials.gov identifier: NCT01199705.

Cost-Effectiveness Analysis of CT Colonography for Colorectal Cancer Screening Program to Working Age in Japan.

OBJECTIVES: To assess the cost-effectiveness of computed tomography colonography (CTC) for a colorectal cancer screening program in a working population (aged 40-60 years) from a health care payer's perspective in Japan. METHODS: A Markov model for colorectal cancer was constructed to estimate the long-term (10-year, 20-year, and 30-year) effect of introducing CTC for three different strategies in the cohort aged 40 years on April 1, 2011. Strategy 1 (the current strategy in Japan): fecal occult blood test (FOBT) followed by optical colonoscopy (OC). In this case, 41.8% of those who were FOBT-positive did not undergo OC (uptake 58.2%). Strategy 2: All FOBT-positive cases would be offered CTC (uptake 79.1%) followed by OC. Strategy 3: Only those FOBT-positive cases who were reluctant to undergo OC (41.8%) would be offered CTC (assumed uptake 50.0%) followed by OC. Epidemiological data were obtained mainly from statistics published by the Japanese National Cancer Center. We set quality-adjusted life-year (QALY) as the primary outcome and colorectal cancer death and expected life-years as secondary ones. The discount rate for both costs and outcomes was set at 3%. RESULTS: In the base-case (20-year) analysis, total cost was increased from Japanese yen (JPY) 65,614 million (strategy 1) to JPY 69,405 million (strategy 2) but was decreased to JPY 63,878 million (strategy 3). The total QALY increased from 28,156,046 QALYs (strategy 1) to 28,158,349 (strategy 2) and 28,159,058 QALYs (strategy 3). Therefore, the incremental cost-effectiveness ratio was JPY 1,646,000 per QALY gained for strategy 2 and strategy 3 was dominant against strategy 1, both of which were well below the Japanese threshold (JPY 5-6 million per QALY gained). CONCLUSION: Adding CTC into the current colorectal cancer screening program for the working population seems to be a cost-effective option.

Analysis of direct medical and nonmedical costs for care of rheumatoid arthritis patients using the large cohort database, IORRA.

OBJECTIVES: Our goal was to determine the annual direct medical and nonmedical costs for the care of patients with rheumatoid arthritis (RA) using data from a large cohort database in Japan. METHODS: Direct medical costs [out of pocket to hospitals and pharmacies and for complementary and alternative medicine (CAM)] and nonmedical costs (caregiving, transportation, self-help devices, house modifications) were determined for RA patients who were participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) studies conducted in October 2007 and April 2008. Correlations between these costs and RA disease activity, disability level, and quality of life (QOL) were assessed. RESULTS: Data were analyzed from 5,204 and 5,265 RA patients in October 2007 and April 2008, respectively. The annual direct medical costs were JPY132,000 [out of pocket to hospital (US$1 = JPY90 in 2007)], JPY84,000 (out of pocket to pharmacy), and JPY146,000 (CAM). Annual direct nonmedical costs were JPY105,000 (caregiving), JPY22,000 (transportation), JPY30,000 (self-help devices), and JPY188,000 (house modifications). Based on the utilization rate for each cost component, the annual medical and nonmedical costs for each RA patient were JPY262,136 and JPY61,441, respectively. Costs increased with increasing RA disease activity and disability level or worsening quality of life (QOL). CONCLUSIONS: Based on the IORRA database, patients with RA bear heavy economic burdens that increase as the disease is exacerbated. The results also suggest that the increase in medical and nonmedical costs may be ameliorated by the proactive control of disease activity.

Funding and infrastructure among large-scale clinical trials examining cardiovascular diseases in Japan: evidence from a questionnaire survey.

BACKGROUND: Large-scale clinical trials with thousands of participants are often needed to evaluate the risk reductions of cardiac events and/or death. Many recent clinical trials have evaluated the incidences of cardiac events using hard endpoints, especially in cardiovascular and metabolic medicine. A high investigation cost is involved in conducting a large-scale clinical trial, and obtaining sufficient funding is essential. The infrastructural environment of clinical trials is currently inadequate in Japan. We conducted a questionnaire-based survey to address this issue. The present study sought to clarify the current situation surrounding large-scale clinical trials in terms of funding and infrastructure, and to inform discussion about improving the financial and infrastructural situation for clinical trials. METHODS: We sent questionnaires to 119 sponsors of large-scale clinical trials between August 2007 and December 2007, and between July 2009 and August 2009. Answers to each question were summarized and data were statistically analyzed. RESULTS: We received responses from the sponsors of 63 (52.9%) out of 119 trials to which questionnaires were sent. The results revealed that 25 trials (39.7%) were funded by foundations, and 21 trials (33.3%) were funded by public agencies. All of the foundations involved in conducting clinical trials, where funding sources were specified, were funded by private organizations such as pharmaceutical companies. All of the clinical trials with a cost of JPY 300 million (USD 3.27 million) or more were funded by private organizations, and none were funded solely by public agencies. The sponsors of 23 trials (36.5%) responded that the trial was 'not registered' to clinical trial registry. CONCLUSIONS: The questionnaire responses revealed that there were still many trials whose funding sources were unclear and many sponsors were unaware of their responsibilities in managing and/or financing the costs of clinical trials. These findings indicate that further discussion is required to establish appropriate frameworks and/or rules regarding funding, while considering conflicts of interest. This discussion should take place as soon as possible to facilitate appropriate clinical trials.

[Pharmacoeconomics of molecular target drugs in Japan].

Various molecular target drugs are developed in recent era in Japan, especially for treatment of cancer, rheumatoid arthritis and other diseases. Although they are much more effective compared to previous drugs, their costs are much more expensive. Thus, pharmacoeconomic analysis in which we evaluate their efficiency, would be highly needed. When we take pharmacoeconomic analyses, we need to assess both costs and health outcomes. In addition, we must compare cost-effectiveness of new interventions and control. To estimate costs of each intervention, not only direct medical costs, but direct non-medical costs (e.g. transportation costs, caregiving costs, house--modification costs) and indirect costs, or productivity losses should be separately calculated and presented. To evaluate efficiencies of anti-rheumatoid biologic agent in Japan, we started to collaborate with large-scale cohort of patient with rheumatoid arthritis in Japan, IORRA cohort in Tokyo Women's Medical University. With this data, we are taking various pharmacoeconomic analysis.

Potentially inappropriate medication use in elderly Japanese patients.

BACKGROUND: Modified Beers criteria for elderly Japanese patients were developed in 2008 by consensus among 9 experts to reflect regional clinical practice and available medications in Japan. Since then, many physicians and pharmacists have expressed interest in obtaining more information about the criteria and alternative drug choices. OBJECTIVE: This study examined the incidence, health care utilization, and costs associated with potentially inappropriate medications (PIMs) in elderly patients based on the modified Beers criteria. METHODS: A retrospective, observational cohort study was conducted using health insurance claims data in Japan. The study population included elderly patients aged >or=65 years who had at least 2 pharmacy claims in separate months over a 1-year period (April 2006 through March 2007). Use of the PIMs was identified using the modified criteria, and 1-year incidence rates were calculated for the total study population and for subgroups stratified by age and sex. A logistic regression model was used to examine demographic and clinical characteristics associated with PIMs. Health care utilization rates and costs were also analyzed and compared between patients with and without PIMs using generalized linear models. All models included dummy variables indicating age category, female sex, hospitalization, polypharmacy, index month, and number of Elixhauser comorbidities to adjust for potential confounders. RESULTS: Among 6628 elderly patients, 71.2% (4721/6628) were female and 62.9% (4167/6628) were aged 65 to 74 years; 43.6% (2889/6628) were prescribed at least one PIM. The most commonly used PIMs were histamine-2 blockers (20.5% [1356/6628]), benzodiazepines (11.4% [756/6628]), and anticholinergics and antihistamines (7.9% [526/6628]). No significant differences in incidence rates were observed based on age or sex. Inpatient service use, polypharmacy, and comorbidities of peptic ulcer, depression, and cardiac arrhythmias were significant predictors of PIM use while controlling for other factors. PIM users had significantly higher hospitalization risk (1.68-fold), more outpatient visit days (1.18-fold), and higher medical costs (33% increase) than did nonusers. CONCLUSIONS: In a group of elderly Japanese patients, 43.6% used at least one PIM over a 1-year period in this study. PIM use was associated with greater health care utilization rates and costs.

Out-of-pocket payment and cost-effectiveness of XELOX and XELOX plus bevacizumab therapy: from the perspective of metastatic colorectal cancer patients in Japan.

OBJECTIVE: The purpose of our study was to estimate the out-of-pocket payment and cost-effectiveness of capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab from the perspective of patients with metastatic colorectal cancer (MCRC). METHODS: Based on the NO16966 and NO16967 trials, the mean out-of-pocket payment was calculated from patient-level data. Out-of-pocket payments for 16 cycles (11 months) of first-line chemotherapy and 8 cycles (5 months) of second-line chemotherapy were included. In addition, incremental cost-effectiveness ratios (ICERs) for first-line bevacizumab were calculated by dividing the difference of the out-of-pocket payment by the difference of the mean number of progression-free survival (PFS) years or quality-adjusted PFS (QAPFS) years. RESULTS: The mean out-of-pocket payments for middle-income patients under 70 years of age were JPY 328,000 for 16 cycles of first-line XELOX and JPY 376,000 for XELOX plus bevacizumab. The mean out-of-pocket payment for 8 cycles of second-line XELOX was calculated to be JPY 175,000. Middle-income patients over 70 years of age were required to pay JPY 61,000 and JPY 72,000 for first-line XELOX and XELOX plus bevacizumab, respectively. The ICERs of middle-income patients <70 years of age were JPY 430,000/PFS-year and JPY 720,000/QAPFS-year, and those of middle-income patients >70 years of age were JPY 100,000/PFS-year and JPY 170,000/QAPFS-year. CONCLUSIONS: We clarified the out-of-pocket payment and cost-effectiveness of chemotherapy of MCRC patients in Japan. Our previous survey shows it is highly possible that many patients prefer to pay that incremental out-of-pocket payment to gain one additional QAPFS year. However, our cost-effectiveness analysis was not conducted from the perspective of society or healthcare payers.

International survey on willingness-to-pay (WTP) for one additional QALY gained: what is the threshold of cost effectiveness?

Although the threshold of cost effectiveness of medical interventions is thought to be 20 000- 30 000 UK pounds in the UK, and $50 000-$100 000 in the US, it is well known that these values are unjustified, due to lack of explicit scientific evidence. We measured willingness-to-pay (WTP) for one additional quality-adjusted life-year gained to determine the threshold of the incremental cost-effectiveness ratio. Our study used the Internet to compare WTP for the additional year of survival in a perfect status of health in Japan, the Republic of Korea (ROK), Taiwan, Australia, the UK, and the US. The research utilized a double-bound dichotomous choice, and analysis by the nonparametric Turnbull method. WTP values were JPY 5 million (Japan), KWN 68 million (ROK), NT$ 2.1 million (Taiwan), 23 000 UK pounds (UK), AU$ 64 000 (Australia), and US$ 62 000 (US). The discount rates of outcome were estimated at 6.8% (Japan), 3.7% (ROK), 1.6% (Taiwan), 2.8% (UK), 1.9% (Australia), and 3.2% (US). Based on the current study, we suggest new classification of cost-effectiveness plane and methodology for decision making.

Cost-effectiveness analysis of KRAS testing and cetuximab as last-line therapy for colorectal cancer.

BACKGROUND: Cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves progression-free survival and overall survival in patients with metastatic colorectal cancer (mCRC). However, patients with a KRAS gene mutation do not benefit from cetuximab therapy. METHODS: We performed a cost-effectiveness analysis of KRAS testing and cetuximab treatment as last-line therapy for patients with mCRC in Japan. In our analysis, we considered three treatment strategies. In the 'KRAS-testing strategy' (strategy A), KRAS testing was performed to guide treatment: patients with wild-type KRAS received cetuximab, and those with mutant KRAS received best supportive care (BSC). In the 'no-KRAS-testing strategy' (strategy B), genetic testing was not conducted and all patients received cetuximab. In the 'no-cetuximab strategy' (strategy C), genetic testing was not conducted and all patients received BSC. To evaluate the cost effectiveness of KRAS testing, the KRAS-testing strategy was compared with the no-KRAS-testing strategy; to evaluate the cost effectiveness of KRAS testing and cetuximab, the KRAS-testing strategy was compared with the no-cetuximab strategy; and to evaluate the cost effectiveness of cetuximab treatment without KRAS testing, the no-KRAS-testing strategy was compared with the no-cetuximab strategy. A three-state Markov model was used to predict expected costs and outcomes for each group. Outcomes in the model were based on those reported in a retrospective analysis of data from the National Cancer Institute of Canada Clinical Trials Group CO.17 study. We included only direct medical costs from the perspective of the Japanese healthcare payer. A 3% discount rate was used for both costs and outcome. Two outcomes, life-years (LYs) gained and quality-adjusted life-years (QALYs) gained, were used to calculate the incremental cost-effectiveness ratio (ICER). RESULTS: Our cost-effectiveness analysis revealed that the KRAS-testing strategy was dominant compared with the no-KRAS-testing strategy, with an expected cost reduction of ¥0.5 million per patient and an estimated budget impact of ¥3-5 billion ($US42-59 million; July 2010 values) per year. The ICER of the KRAS-testing strategy compared with the no-cetuximab strategy was ¥11 million ($US120 000) per LY gained and ¥16 million ($US160 000) per QALY gained, whereas the ICER of the KRAS-testing strategy compared with the no-KRAS-testing strategy was ¥14 million ($US180 000) per LY gained and ¥21 million ($US230 000) per QALY gained. These results were supported by the sensitivity analysis. CONCLUSIONS: KRAS testing is recommended before administering cetuximab as last-line therapy for patients with mCRC. However, our analysis suggests that the ICER of cetuximab treatment (with or without KRAS testing) is too high, even if treatment is limited to patients with wild-type KRAS.

Cost-effectiveness analysis of capecitabine compared with bolus 5-fluorouracil/l-leucovorin for the adjuvant treatment of colon cancer in Japan.

OBJECTIVE: A cost-effectiveness analysis of oral capecitabine versus intravenous bolus 5-fluorouracil/l-leucovorin (FU/LV) as adjuvant therapy in patients with stage 3 colon cancer was performed from a Japanese healthcare payer perspective. METHODS: Adjuvant therapy comprised 24 weeks of treatment with either oral capecitabine 1250 mg/m(2) twice daily on days 1-14 of a 21-day cycle or intravenous bolus FU 500 mg/m(2) and LV 250 mg/m(2) weekly for 6 weeks of an 8-week cycle (Roswell Park regimen). The analysis comprised short-term (1 year after initiation of adjuvant therapy) and long-term (up to 15 years) components. The long-term analysis involved a three-state (disease-free, recurrence and death) Markov model. Estimates for transition probabilities, costs and utilities were derived from the X-ACT trial, a Japanese phase II trial, and other published sources. Cost estimates were considered from the perspective of a healthcare payer. Costs were expressed in Japanese Yen (yen), year 2007 values. A discount rate of 3% was applied to costs and outcomes. Cost effectiveness was expressed as a cost per QALY. The effects of uncertainty were explored through one-way and probabilistic sensitivity analyses. RESULTS: In the 1-year analysis, direct costs were yen440,000 ($US4000) less per patient with capecitabine than with FU/LV. In the long-term analysis, differences between treatments in direct medical costs ranged from yen470,000 ($US4300) to yen580,000 ($US5300) depending on the time horizon used. Capecitabine was also projected to increase the number of QALYs compared with FU/LV. The sensitivity analysis suggested that the model outcome was robust. The probabilistic sensitivity analysis estimate of capecitabine being the dominant regimen was 96.6% at a zero willingness to pay. Direct costs remained lower with capecitabine if the price of generic LV was >OR=50% of the branded product. CONCLUSION: This analysis suggests that capecitabine improves health outcomes and lowers direct costs compared with bolus FU/LV (i.e. dominant treatment strategy) when used as adjuvant therapy in patients with stage 3 colon cancer in Japan.

Health utility scores of colorectal cancer based on societal preference in Japan.

PURPOSE: We measured health utility scores of colorectal cancer (CRC) patients from a societal perspective in Japan. METHODS: Twenty-five states of health were described: four metastatic states without severe adverse events (AEs), 16 metastatic states with Grade 3/4 AEs, four adjuvant states, and one terminal state. A total of 1,500 respondents stratified by age and gender were recruited randomly from the largest Web-panel in Japan. Respondents were allocated randomly to three of the 25 health states and answered questionnaires by standard gamble (SG) and time trade-off (TTO) methods. RESULTS: Although utility scores of metastatic CRC receiving XELOX (capecitabine plus oxaliplatin) chemotherapy were 0.48(SG and TTO) (with stoma) and 0.57(SG) or 0.59(TTO) (without stoma), utility scores of those receiving FOLFOX4 (5-fluorouracil/folinic acid and oxaliplatin) chemotherapy were 0.42(SG) or 0.43(TTO) (with stoma) and 0.52(SG) or 0.53(TTO) (without stoma). These differences between XELOX and FOLFOX4 were statistically significant (P = 0.0198 in SG and P = 0.0059 in TTO). Stage 3/4 AEs decreased utility scores to 0.35-0.4 and 0.4-0.45 in the presence and absence of stoma, respectively. CONCLUSIONS: XELOX was generally considered a significantly preferable chemotherapy regimen compared to FOLFOX4 for CRC in Japan. Almost all Grade 3/4 AEs and stoma significantly decreased utility scores. These differences are dependent on the accuracy of the health state description and to confirm these results. In future research, it would be preferable that preference-based HRQoL measures are used directly in patients if utility scores are practically measurable by such method.

Cost-utility analysis of varenicline, an oral smoking-cessation drug, in Japan.

OBJECTIVE: To conduct a cost-utility analysis of two 12-week smoking-cessation interventions in Japan: smoking-cessation counselling by a physician compared with use of varenicline, an oral smoking-cessation drug, in addition to counselling. METHODS: A Markov model was constructed to analyse lifetime medical costs and QALYs from the perspective of the healthcare payer. The cycle length was 5 years. Both costs and QALYs were discounted at 3% annually. The cohort of smokers was classified by sex and age, and we assumed that smokers started smoking at the age of 20 years and received smoking-cessation therapy at the ages of 30, 40, 50, 60 or 70 years (five separate models were run). The healthcare costs and QALYs were calculated throughout the term until the age of 90 years. In the base-case analysis, success rates of varenicline plus counselling and counselling alone were assumed to be 37.9% and 25.5%, respectively, in male smokers, and 22.2% and 16.1%, respectively, in female smokers, based on a randomized controlled trial conducted in Japan. Both univariate and probabilistic sensitivity analyses were conducted. RESULTS: Prescribed varenicline was shown to be more effective and less costly than smoking-cessation counselling alone. Varenicline would save direct medical costs of Japanese Yen (yen)43 846 ($US381; $US1 = yen115; Oct 2007) and generate an increase of 0.094 QALYs in male smokers. In females the incremental cost-effectiveness ratio was yen346 143 per QALY gained. Varenicline is estimated to save yen23.7 billion ($US206 million) of the medical costs for tobacco-associated diseases for the whole population. Overall savings are yen9.5 billion. Sensitivity analyses suggested the robustness of the results. CONCLUSIONS: As with any data of this nature, there is some uncertainty in the results and further research is warranted. However, based on the results of this pharmacoeconomic evaluation, varenicline, the first non-nicotine, oral treatment developed for smoking cessation, appears to be cost effective and may contribute to future medical cost savings in Japan.

[Study on the history of exchange in pharmaceutical science between Japan and Korea after the Modern period: focus on Korean students sent to Japan with expenses funded by the Japanese government].

According to an old historical text, Nihonshoki [Chinese and Korean characters: see text]), there are records of medical doctors ([Chinese and Korean characters: see text]) and herbal pharmacists ([Chinese and Korean characters: see text]) being dispatched to Japan as early as 554 A.D. ([Chinese and Korean characters: see text]). More recently, a clinic ([Chinese and Korean characters: see text]) for Japanese residents in Pusan was established in 1877. Advanced modern pharmacy from Japan began to be introduced to Korea after 1909. Based on an agreement between the Korean and Japanese governments, Korean students sent to Japan with expenses funded by the Japanese government became a systematic program after 1965. As a result, Koreans who earned Ph.D.s from Japanese universities became a majority in the faculties of Korean schools of pharmacy. However, this trend drastically shifted in the years after 1990, at which time the primary nation for earning Ph.D.s became the United States; the number of students studying in Japan has become very low recently. In this study, six ex-students who studied in Japan were interviewed and the results were analyzed. Furthermore, the past, present and future perspectives of Korean students in Japan were discussed while focusing on the system of Korean students being sent to Japan with expenses funded by the Japanese government.

[Regulatory sciences in herbal medicines and dietary supplements].

Regulatory science began in the late 1980's in the pharmaceutical area in Japan. It aimed not only at vertical, top-down regulation but also horizontal regulation to suit the social value system. Herbal medicines and dietary supplements are two areas where regulatory science is still not well developed and used. Risk perception, risk assessment and risk management in these areas are often neglected by regulators, academicians and the public. Since the risk of using herbal medicines and dietary supplements is a global concern, development of a global regulatory system is needed. In this paper, we introduce the current situation of several projects which deal with regulatory science in herbal medicines and dietary supplements, namely: (1) Herbal ATC (HATC) classification project initiated by Uppsala Monitoring Centre (UMC) which led to the development of the provisional HATC code of 228 Kampo formulae and Standard Kampo Formula Nomenclature (SKFN) in Japan, (2) WHO/WPRO International Standardization of Terminology (IST) which resulted in the publication of "WHO Internal Standard Terminologies on Traditional Medicine in the Western Pacific Region Forum for Herbal Harmonization", (3) Forum for the Harmonization of Herbal Medicines (FHH), (4) CONSORT extension for herbal medicines, (5) ICH M5 (Data elements and standards for drug dictionaries), and (6) activities on nomenclature at the International Organization for Standardization (ISO). However, there is a lack of coordination among these projects. Therefore, harmonization of all projects aimed at harmonizing and standardizing all aspects of regulatory science for herbal medicines and dietary supplements is recommended. However, careful consideration should be given to each unique local situation.