[Establishment of Mono-scaled Benefit/Risk Analysis of HPV Vaccine].

Decisions concerning approval of human papillomavirus (HPV) vaccines and their use are based on expert evaluation of the vaccines. However, the quantitative differences between vaccine benefits and risks are difficult for non-experts to understand. In this study, we developed a new method to calculate the benefits and risks of the HPV vaccines using disability-adjusted life year (DALY) as the mono-scaled weight for various benefits and risks relevant to the vaccines. We evaluated benefits as a gain of DALY values for cervical cancer and risks as the loss of DALY values for various adverse events by the vaccination. To calculate the loss of DALY values, we integrated all adverse events in the International Classification of Diseases chapters. The novel method reflected the men-women ratio of this epidemiological disease to a certain extent. Among the vaccinated women, 111372 and 477190 received a bivalent and quadrivalent vaccine, respectively. The DALY rate of cervical cancer was 148.7. The calculated benefit for the bivalent and quadrivalent vaccines was 149.1 and 638.8, respectively, and set as the theoretical maximum. The risk was calculated as 129.3 and 49.6 in the bivalent and quadrivalent vaccines, respectively. Since HPV vaccines prevent several other cancers, the benefit of the vaccination extends beyond the risk according to this new method.

Burden of caring for Alzheimer's disease or dementia patients in Japan, the US, and EU: results from the National Health and Wellness Survey: a cross-sectional survey.

AIMS: The growing prevalence of Alzheimer's disease (AD) worldwide has sparked the implementation of national policies to support the growing burden among caregivers of AD/dementia patients. This study aims to quantify and compare the burden of AD/dementia caregivers and evaluate how different living arrangements might impact health outcomes among caregivers in Japan, five European countries (5EU), and the United States (US). MATERIALS AND METHODS: This is a cross-sectional study based on existing data from the 2018 National Health and Wellness Survey. Health outcome measures included health-related quality of life (HRQoL), health state utilities, work productivity and activity impairment (WPAI), and measurement of depression and anxiety amongst AD/dementia caregivers and non-caregivers. Pairwise comparisons between AD/dementia caregivers in Japan, 5EU, and the US were conducted. Multivariate analysis was used to compare across groups within each region, with adjustment for potential confounding effects. RESULTS: A higher proportion of caregivers of AD/dementia patients in Japan were 65 years or older as compared to 5EU and US. On the contrary, female caregivers were significantly higher in the US than Japan and 5EU. The HRQoL and health state utilities index scores amongst AD/dementia caregivers were highest in Japan and lowest in the US. Caregivers in Japan incurred the lowest WPAI among the three regions. The proportion of AD/dementia patients reportedly living in an institution was highest in Japan as compared to the US and EU. Notably, US caregivers whose patients lived in an institution experienced significantly less caregiving burden as compared to caregivers whose patients lived in the community. CONCLUSIONS: The caregiving burden among AD/dementia caregivers was substantial across the three regions, with similarities and differences between the West and Japan. The lower caregiving burden in Japan was potentially associated with national policies supporting long-term healthcare and institutionalized nursing care facilities for AD/dementia patients.

Alternative New Mono-scaled Quantitative Benefit-Risk Assessment of Human Papillomavirus Vaccine in Japan.

BACKGROUND: The human papillomavirus (HPV) vaccine coverage is very low in Japan since the government suspended the active encouragement of the vaccination. We aimed to conduct a benefit-risk assessment of HPV vaccination and explore different consequent scenarios to identify potential improvements to the current Japanese immunization program. METHODS: To calculate social benefit-risk of HPV vaccine, we used the Markov model to represent the natural history of HPV and adverse events (AEs) using disability-adjusted life year (DALY) as the outcome. Benefits and risks were calculated as the sum of negative and positive outcomes corresponding to all preventable diseases and AEs associated with HPV vaccination, respectively. The benefit-risk balance in 2050 was estimated using published data. RESULTS: Our model was confirmed by published cervical cancer incidence and mortality rates. The benefit-risk balance in 2050 showed that the most effective scenario was the introduction of 9-valent HPV vaccine targeting female individuals aged 10-29 years for routine vaccination starting in 2020, although there is possibility of increased risks of AEs for the vaccinated age group post resumption of recommendations. CONCLUSION: Our benefit-risk assessment of HPV vaccine helped estimate various scenarios pertaining to HPV vaccination and identify the best strategy regarding HPV vaccination. This benefit-risk assessment approach may be used for other vaccines and vaccination programs.

Factors associated with humanistic burden and indirect cost among patients with cancer in Japan.

AIMS: Patients with cancer experienced reduced health-related quality-of-life (HRQoL), increased work productivity and activity impairment (WPAI), and indirect costs. With the current emphasis on economic evaluation of health technology in Japan, it is important to understand how indirect costs correlate with HRQoL and patient characteristics. It is also crucial to assess the patient characteristics associated with the HRQoL, WPAI, and indirect costs among patients with any types of cancer. MATERIALS AND METHODS: This cross-sectional study used data from the 2017 Japan National Health and Wellness Survey (NHWS). Respondents self-reported their HRQoL and WPAI by answering validated SF-12v2 and WPAI questionnaires, respectively. Indirect costs were derived using the human capital method. Correlation between HRQoL components and indirect costs were assessed using Spearman's rank-order correlation. Correlation between patient characteristics and HRQoL, WPAI, and indirect costs were analyzed using generalized linear models. RESULTS: A total of 1,540 patients with any types of cancer, 254 with breast cancer, and 144 with colorectal cancer were included in the analyses. There was significant negative correlation between the indirect costs and HRQoL components among patients with any types of cancer. Patients with lower comorbid burden, higher household income, employed, married, or living with partner, never smokers, and exercised tended to have higher HRQoL. Being never smokers, having lower comorbid burden, normal weight, and exercised were associated with lower WPAI measures. Additionally, patients who were older, not married, not obese, and not smoking tended to incur lower indirect costs. CONCLUSIONS: The negative correlation between HRQoL and indirect costs among patients with cancer emphasized the needs to improve health outcomes and reduce indirect costs of patients. The factors associated with cancer burden identified in this study provide insights to allow targeted intervention to improve HRQoL and lessen the WPAI and indirect cost among cancer patients in Japan.

Weather Fluctuations May Have an Impact on Stroke Occurrence in a Society: A Population-Based Cohort Study.

BACKGROUND: Stroke has been found to have a seasonally varying incidence; blood pressure, one of its risk factors, is influenced by humidity and temperature. The relationship between the incidence of stroke and meteorological parameters remains controversial. OBJECTIVE: We investigated whether meteorological conditions are significant risk factors for stroke, focusing on the fluctuation of weather elements that triggers the onset of stroke. METHODS: We collected ambulance transportation data recorded by emergency personnel from Gifu Prefecture. We included cases where the cause of the transportation was stroke and excluded cases of trauma. We combined these data with meteorological data as well as data on average temperature, average air pressure, and humidity provided publicly by the Japan Meteorological Agency. Our target period was from January 2012 to December 2016. RESULTS: In the 5-year target period, there were 5,501 occurrences of ambulance transportation due to stroke. A seasonal tendency was confirmed, since ambulance transportation for stroke occurred more frequently at low temperatures (p < 0.001). Temperature (odds ratio: 0.91; p < 0.001) and humidity change (odds ratio: 1.50; p = 0.016) were identified as risk factors for ambulance transportation due to stroke. An increase in temperature incurs a lower risk than a decrease (odds ratio: 0.58; p = 0.09), although there is no statistically significant difference. CONCLUSIONS: Meteorological effects on the frequency of ambulance transportation due to stroke were studied. A lower temperature and radical humidity change were identified as risk factors for ambulance transportation due to stroke, and a decrease in temperature was also associated. We speculate on the possibilities of using meteorological data to optimize the assignment of limited medical resources in medical economics.

A population-based study of the humanistic burden among cancer patients in Japan.

Aims: Understanding the burden of cancer in Japan is becoming increasingly important to address the socio-economic consequences of the disease. This study broadly examined the cancer burden in terms of: Health-Related Quality of Life (HRQoL), work productivity and activity impairment (WPAI), stress-related comorbidities, and indirect costs in patients diagnosed with (i) any type of cancer, (ii) breast cancer, (iii) colorectal cancer, compared to controls without cancer.Materials and methods: This cross-sectional study used data from the 2017 Japan National Health and Wellness Survey (NHWS). Patient outcomes included self-reported stress-related comorbidities, HRQoL assessed by Short Form 12-item Health Survey and EuroQoL 5-dimension scale (EQ-5D), and work productivity and indirect costs assessed by WPAI questionnaire. Multivariate analysis was performed to compare outcomes across groups. An ad-hoc analysis compared respondents currently and currently not receiving prescription medication (Rx).Results: A total of 1,540 patients with any type of cancer, 254 with breast cancer, 144 with colorectal cancer were included in the analyses and compared to 28,070 controls without cancer. After adjusting for potential confounding effects patients with any type of cancer had significantly lower mental component summary scores (45.70 vs. 46.45, p = .003), physical component summary scores (48.95 vs. 50.02, p < .001) and EQ-5D index (0.77 vs. 0.79, p < .001), and significantly increased absenteeism (5.13% vs. 2.68% p < .001) compared to controls. No significant differences were detected for indirect costs. Breast cancer patients had significantly increased odds of anxiety and migraine. Colorectal cancer patients had significantly increased odds of insomnia. Patients currently receiving Rx had significantly lower HRQoL and higher WPAI than both controls and cancer patients not receiving Rx.Conclusions: Japanese cancer patients experience a significantly decreased HRQoL, increased absenteeism and higher odds ratio for stress-related comorbidities. This has implications for future policy making and Health Technology Assessment in Japan.

Humanistic and economic burden among caregivers of patients with cancer in Japan.

Aims: As the number of cancer patients increases in Japan, and people are living longer with cancer, the need for caregivers of cancer patients is expected to increase substantially. This study intended to reveal the humanistic and economic burden among caregivers of cancer patients, and to compare it with the burden among caregivers of patients with other conditions (other caregivers) and non-caregivers.Materials and methods: This cross-sectional analysis used data from the Japan National Health and Wellness Survey 2017. Outcome measures included the Short Form 12-item Health Survey for health-related quality of life (HRQoL), EuroQol 5-dimension scale (EQ-5D) for health states utilities, Work Productivity and Activity Impairment questionnaire for the impact of health on productivity and activity, and indirect costs. Multivariate analysis was used to compare across groups, with adjustment for potential confounding effects.Results: A total of 251 caregivers of cancer patients, 1,543 other caregivers, and 27,300 non-caregivers were identified. Caregivers of cancer patients (average 48.0 years old) tended to be younger than non-caregivers (51.5) and other caregivers (54.4) and had the highest education level (57.8% completed university education). Fewer non-caregivers had stress-related comorbidities than caregivers. Non-caregivers had significantly higher EQ-5D index scores than caregivers (average 0.81 vs. 0.73 vs. 0.74). Caregivers of cancer patients had significantly lower mental component summary scores than non-caregivers (40.18 vs. 46.70), and the difference indicated a clinically meaningful decrease in HRQoL. Caregivers of cancer patients had significantly higher presenteeism (37.31% vs. 20.43%), total work productivity impairment (38.85% vs. 21.98%), and activity impairment (40.94% vs. 25.78%) than non-caregivers. Additionally, caregivers of cancer patients had significantly higher total indirect costs (36.34% vs. 20.03% of average annual income).Conclusions: These results have implications for future healthcare planning, suggesting the importance of healthcare systems in Japan to consider the substantial burden borne by caregivers of cancer patients.

Health Technology Assessment in Japan: A Pharmaceutical Industry Perspective.

BACKGROUND: Japan has been preparing to implement a Health Technology Assessment (HTA) process in 2018. Through a 2-year pilot program implemented in 2016, the government examined the criteria for applicable products and the necessary infrastructure to review both the content and quality of the data and to conduct cost-effectiveness assessments to be incorporated into the current Japanese reimbursement and pricing scheme. A survey of the pharmaceutical industry was conducted to understand the current landscape and to identify issues and challenges of implementing HTA in Japan. METHODS: A semi-structured 19-item questionnaire was designed, and a survey was conducted via face-to-face or phone interviews. Answers were transcribed in English after the interviews and confirmed by e-mail. The survey focuses on pharmaceutical companies that develop new innovative products to be associated with the planned HTA. RESULTS: Differences between Japanese and global pharmaceutical companies were observed in terms of dedicated HTA teams in place, the use of quality of life data, and relationships with external vendors. Addressing a shortage of HTA professionals in Japan is critical to implement HTA. The survey found that list prices compared to those proposed by companies was an issue. CONCLUSIONS: Although the government decided to implement HTA for the pricing scheme in 2018, a shortage of experts and researchers remains a challenge. Findings suggest HTA should not be used solely to reduce pharmaceutical spending, as the impact by the HTA implementation will be temporary and discourage innovation.

Industry Perspective of Pediatric Drug Development in the United States: Involvement of the European Union Countries.

BACKGROUND: Efforts to promote the development of pediatric pharmacotherapy include regulatory frameworks and close collaboration between the US Food and Drug Administration and the European Medicines Agency. We characterized the current status of pediatric clinical trials conducted in the United States by the pharmaceutical industry, focusing on the involvement of the European Union member countries, to clarify the industry perspective. METHODS: Data on US pediatric clinical trials were obtained from ClinicalTrials.gov . Binary regression analysis was performed to identify what factors influence the likelihood of involvement of European Union countries. RESULTS: A total of 633 US pediatric clinical trials that met inclusion criteria were extracted and surveyed. Of these, 206 (32.5%) involved a European Union country site(s). The results of binary regression analysis indicated that attribution of industry, phase, disease area, and age of pediatric participants influenced the likelihood of the involvement of European Union countries in US pediatric clinical trials. Relatively complicated or large pediatric clinical trials, such as phase II and III trials and those that included a broad age range of participants, had a significantly greater likelihood of the involvement of European Union countries ( P < .05). CONCLUSION: Our results suggest that (1) the pharmaceutical industry utilizes regulatory frameworks in making business decisions regarding pediatric clinical trials, (2) disease area affects the involvement of European Union countries, and (3) feasibility of clinical trials is mainly concerned by pharmaceutical industry for pediatric drug development. Additional incentives for high marketability may further motivate pharmaceutical industry to develop pediatric drugs.

Identification of Drug Characteristics for Implementing Multiregional Clinical Trials Including Japan.

PURPOSE: Multiregional clinical trials (MRCT) are a standard strategy used to improve global drug approval efficiency and the feasibility of clinical trials. Japan is the world's third largest drug market with a unique health care system, making it a key inclusion as an operational region for MRCT (MRCT-JP) for global drug development. We aimed to identify the factors required for efficient drug development by comprehensively reviewing the clinical trials of drugs approved in Japan to identify the factors associated with whether or not MRCT-JP is implemented. METHODS: We surveyed the review reports and summaries of application data published by the Pharmaceuticals and Medical Devices Agency. We identified drugs for which the clinical trial data package included MRCT-JP and selected the same number of drugs for which the clinical trial data package did not include MRCT-JP from the most recent survey period for comparison. We also examined other publication information, in addition to the review reports, as necessary. The influence of each explanatory variable was analyzed by logistic regression analysis, with whether or not MRCT-JP was implemented as the explanatory variable. Statistical significance was set at 5%. FINDINGS: In the survey period up to September 2017, 165 drugs developed with MRCT-JP were approved for manufacture and sale in Japan. "Respiratory system," "inhalation," "biological drug," and "under review" evaluation status for the United States, European Union, and other areas, "approved" evaluation status for the United States, "new ingredients," "priority review," "non-Japanese firm," and "Top 1-10" and "Top 11-20" drug sales rankings for pharmaceutical companies were identified as potential factors leading to the implementation of MRCT-JP. In contrast, "general anti-infectives for systemic use," "various," "external," "chemical compound," "unsubmitted" evaluation status for both the United States and European Union, and "Top 51+" drug sales rankings were potential factors for not implementing MRCT-JP. IMPLICATIONS: Therapeutic classification and agent type, in addition to capital type and United States and European Union evaluation status suggested by a previous study, were associated with implementing MRCT-JP. It is important to determine the best way to utilize MRCT-JP to maximize the value of products. Our findings were based on successful cases and may therefore be helpful for designing clinical development plans. Appropriate use of MRCT-JP will improve productivity in the pharmaceutical industry.