Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab Combination Therapy as First-line Treatment for Advanced Renal Cell Carcinoma in Japan.

OBJECTIVES: The purpose of this study is to examine the cost-effectiveness of nivolumab (NIVO) plus ipilimumab (IPI) combination therapy (NIVO + IPI) compared with the sunitinib (SUN) therapy for Japanese patients with advanced renal cell carcinoma from the perspective of a Japanese health insurance payer. METHODS: A lifetime horizon was applied, and 2% per annum was set as the discount rate. The threshold was set as $ 75 000 per quality-adjusted life-year (QALY) gained. For the analytical method, we used a partitioned survival analysis model to estimate the incremental cost-effectiveness ratio (ICER), which is calculated by dividing incremental costs by incremental QALYs. Progression-free survival, progressive disease, and death were set as health states. Additionally, cost parameters and utility weights were set as key parameters. We set the intermediate/poor-risk population as the base case. Scenario analysis was conducted for the intention-to-treat population and the favorable risk population. Furthermore, one-way sensitivity analysis and probabilistic sensitivity analysis were conducted for each population. RESULTS: In the base-case analysis, the QALYs of NIVO + IPI and SUN were 4.32 and 2.99, respectively. NIVO + IPI conferred 1.34 additional QALYs. Meanwhile, the total costs in the NIVO + IPI and SUN were $692 288 and $475 481, respectively. As a result, the ICER of NIVO + IPI compared with SUN was estimated to be $162 243 per QALY gained. The parameter that greatly affected the ICER was the utility weight of progression-free survival in NIVO + IPI. CONCLUSIONS: NIVO + IPI for advanced renal cell carcinoma seems to be not cost-effective compared with the SUN in the Japanese healthcare system.

Cost-Effectiveness of First-Line Nivolumab Plus Ipilimumab Combination Therapy in Advanced Non-Small-Cell Lung Cancer in Japan.

BACKGROUND AND OBJECTIVE: In Japan, indications for nivolumab have been expanded to include the combination therapy with ipilimumab in various cancers. This study aimed to evaluate the cost-effectiveness of combination therapy of nivolumab plus ipilimumab (NIV + IPI) for patients with advanced non-small-cell lung cancer (NSCLC), comparing it with platinum-doublet chemotherapy in Japanese settings. METHODS: A partitioned survival model was developed to predict costs and quality-adjusted life-years (QALYs) in a NIV + IPI arm and a chemotherapy arm. Data on overall survival and progression-free survival were derived from the CheckMate 227 trial. Cost estimates were based on a Japanese healthcare system perspective using real-world data from the JMDC claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of NIV + IPI therapy compared with chemotherapy was estimated. A scenario analysis on the level of programmed death-ligand 1 (PD-L1) expression was conducted. In addition, sensitivity analyses were performed to assess the uncertainty in parameter settings. RESULTS: Compared with chemotherapy, NIV + IPI therapy incurred an additional cost of USD102,623 and conferred an additional 1.007 QALY, which resulted in an ICER of USD101,950/QALY gained. Contrary to prior expectations, the ICER of patients with a PD-L1 expression level ≥ 1% was higher than that of patients with a PD-L1 expression level < 1% (USD145,868/QALY and USD127,737/QALY, respectively). Sensitivity analyses showed a relatively robust result with the ICERs remaining higher than a Japanese price adjustment threshold of USD75,000/QALY with a few exceptions. CONCLUSIONS: The combination of NIV + IPI as first-line therapy would not be cost effective under a willingness-to-pay threshold of USD75,000/QALY from the perspective of the Japanese healthcare system.

Economic Evaluations of Gestational Diabetes Mellitus Screening: A Systematic Review.

BACKGROUND: This study aims to find evidence of the cost-effectiveness of gestational diabetes mellitus (GDM) screening and assess the quality of current economic evaluations, which have shown different conclusions with a variation in screening methods, data sources, outcome indicators, and implementation in diverse organizational contexts. METHODS: Embase, Medline, Web of Science, Health Technology Assessment, database, and National Health Service Economic Evaluation Database databases were searched through June 2019. Studies on economic evaluation reporting both cost and health outcomes of GDM screening programs in English language were selected, and the quality of the studies was assessed using Drummond's checklist. The general characteristics, main assumptions, and results of the economic evaluations were summarized. RESULTS: Our search yielded 10 eligible economic evaluations with different screening strategies compared in different settings and perspectives. The selected papers scored 81% (68-97%) on the items in Drummond's checklist on average. In general, a screening program is cost-effective or even dominant over no screening. The one-step screening, with more cases detected, is more likely to be cost-effective than the two-step screening. Universal screening is more likely to be cost-effective than screening targeting the high-risk population. Parameters affecting cost-effectiveness include: diagnosis criteria, epidemiological characteristics of the population, efficacy of screening and treatment, and costs. CONCLUSIONS: Most studies found GDM screening to be cost-effective, though uncertainties remain due to many factors. The quality assessment identified weaknesses in the economic evaluations in terms of integrating existing data, measuring costs and consequences, analyzing perspectives, and adjusting for uncertainties.

Inability to control gestational weight gain: an interpretive content analysis of pregnant Chinese women.

OBJECTIVE: This study aims to explore barriers to controlling gestational weight gain in pregnant Chinese women. DESIGN: Data were collected through semistructured interviews with pregnant women experiencing excessive gestational weight gain who struggled with weight management, and the data were examined using an interpretive content analysis. SETTINGS AND PARTICIPANTS: Fifty participants (≥18 years, with excessive gestational weight gain) were recruited when they visited the hospital for antenatal health checkups in Wuhan city (n=36) and Jinan city (n=14) between September and October 2018. RESULTS: Interpretive content analysis identified 75 barriers after examining diet, physical activity levels and general issues stemming from knowledge and beliefs, and physical, social, logistical, emotional and structural characteristics. Compared with reported deductive codes, this study inductively extracted 15 new codes. The most frequent codes showed that expectant grandparents greatly influenced pregnant women's lifestyles, through overprotection, traditional and conservative ideas and practices, and a lack of reliable knowledge or acceptable guidance on gestational weight control. CONCLUSIONS: This study provides a better understanding of the most important obstacles faced during decision making about gestational weight control in Chinese settings, especially the influence of traditional ideas/practices and expectant grandparents. Identifying the specific barriers to weight control should facilitate potential tailored supportive interventions. More efforts on health education for the whole family and a better use of maternal handbooks would be particularly beneficial.

The burden of disease and the cost of illness attributable to child maltreatment in Japan: long-term health consequences largely matter.

BACKGROUND: Child maltreatment leads to enormous adverse short- and long-term health outcomes. The aim of this study is to estimate the burden of disease and the cost of illness attributable to child maltreatment in Japan. METHODS: An incidence-based top-down cost of illness analysis was conducted to estimate medical costs and burden of disease attributable to child maltreatment based on a societal perspective. The assessment included short-term and long-term medical costs and burden of disease measured by Disability-Adjusted Life Years (DALYs) that generates mortality and morbidities, based on several national surveys and systematic review. We considered the main types of child maltreatment as exposure, for which the incidence was obtained from literature review. Based on population attributable fractions (PAFs), burden of disease of physical and mental health consequences attributable to child maltreatment were estimated. Then DALYs were converted into monetary value. The lifetime economic burden was finally estimated by combining with medical costs and subject to sensitivity analysis. RESULTS: The lifetime disease burden expressed in DALYs was estimated at 1,047,580 DALYs (95% CI 788,388 - 1326,80 DALYs) for the cohort victims in 2016. Based on the incidence according to literature review, the overall lifetime economic burden was 50.24 billion USD, equivalent to 1.3 million times of gross domestic product (GDP) per capita. Among the total economic burden, costs of suffering and pain based on DALYs were accounting for 81.3%. These estimates were 7-8 times of conservative estimates which used incidence data from official reported cases. CONCLUSIONS: This study found that the national lifetime cost was huge and equivalent to 1.3 million GDP per capita, and its burden of disease was approximately equal to that of colon and rectum cancers or stomach cancer. Our findings particularly in terms of revealed the considerable burden of disease in long term and potential effects of the strengthened maternal and child care as the preventive strategy.

Coronary heart disease and stroke disease burden attributable to fruit and vegetable intake in Japan: projected DALYS to 2060.

BACKGROUND: Fruit and vegetable consumption was considered a protective effect against cardiovascular and cerebrovascular diseases (CVDs). This study aimed to project the reduction in the CVD burden under different scenarios of increased fruit and vegetable intake in Japan by 2060. METHODS: Population attributable fractions (PAF) were calculated by gender and age in 2015. The projection considered five scenarios for 2015, 2030, 2045, and 2060: 1) a baseline of no changes in intake; 2) a moderate increase in fruit intake (extra 50 g/day or 1/2 serving); 3) an high increase in fruit intake (extra 100 g/day or 1 serving); 4) a moderate increase in vegetable intake (extra 70 g/day or 1 serving); and 5) an high increase in vegetable intake (extra 140 g/day or 2 servings). Potentially preventable disability-adjusted life years (DALYs) for CVDs were estimated for each scenario. Monte Carlo simulations were performed to calculate the 95% confidence intervals of the estimates. RESULTS: Across all age groups, men had a higher daily vegetable intake than women (292.7 g/d > 279.3 g/d) but a lower daily fruit intake (99.3 g/d < 121.0 g/d). Comparing with recommended intake level (350 g/d of vegetable and 200 g/d of fruit), the total CVD burden was estimated to be 302,055 DALYs attributable to inadequate fruit consumption in 2015, which accounted for 12.6% of the total CVD burden (vegetable: 202,651 DALYs; 8.5%). In 2060, the percentage of the CVD burden due to insufficient intake of fruit is estimated to decrease to 7.9% under the moderate increase scenario and to decrease to 4.5% under the high increase scenario (vegetable: 5.4%; 2.4%). CONCLUSIONS: The study suggested that a relevantly large percentage of the CVD burden can be alleviated by promoting even modest increases in fruit and vegetable consumption in Japan.

Correction to: Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

After the publication of our article [1] we have been made aware of a number of mislabelling and reporting errors, which were introduced in the preparation of the manuscript. The conclusions are not affected by these errors and thus remain unchanged.

Cost-effectiveness analysis of different types of human papillomavirus vaccination combined with a cervical cancer screening program in mainland China.

BACKGROUND: China has a high prevalence of human papillomavirus (HPV) and a consequently high burden of disease with respect to cervical cancer. The HPV vaccine has proved to be effective in preventing cervical cancer and is now a part of routine immunization programs worldwide. It has also proved to be cost effective. This study aimed to assess the cost-effectiveness of 2-, 4-, and 9-valent HPV vaccines (hereafter, HPV2, 4 or 9) combined with current screening strategies in China. METHODS: A Markov model was developed for a cohort of 100,000 HPV-free girls to simulate the natural history to HPV infection. Three recommended screening methods (1. liquid-based cytology test + HPV DNA test; 2. pap smear cytology test + HPV DNA test; 3. visual inspection with acetic acid) and three types of HPV vaccination program (HPV2/4/9) were incorporated into 15 intervention options, and the incremental cost-effectiveness ratio (ICER) was calculated to determine the dominant strategies. Costs, transition probabilities and utilities were obtained from a review of the literature and national databases. One-way sensitivity analyses and threshold analyses were performed for key variables in different vaccination scenarios. RESULTS: HPV9 combined with screening showed the highest health impact in terms of reducing HPV-related diseases and increasing the number of quality-adjusted life years (QALYs). Under the current thresholds of willingness to pay (WTP, 3 times the per capita GDP or USD$ 23,880), HPV4/9 proved highly cost effective, while HPV2 combined with screening cost more and was less cost effective. Only when screening coverage increased to 60% ~ 70% did the HPV2 and screening combination strategy become economically feasible. CONCLUSIONS: The combination of the HPV4/9 vaccine with current screening strategies for adolescent girls was highly cost-effective and had a significant impact on reducing the HPV infection-related disease burden in Mainland China.

Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

BACKGROUND: Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. METHODS: An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) compared to status quo. RESULTS: In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. CONCLUSIONS: RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

Cost-effectiveness and Health Benefits of Pediatric 23-valent Pneumococcal Polysaccharide Vaccine, 7-valent Pneumococcal Conjugate Vaccine and Forecasting 13-valent Pneumococcal Conjugate Vaccine in China.

BACKGROUND: Each year in China, approximately 700,000 children under 5 years old are diagnosed with pneumonia, and 30,000 die of the disease. Although 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent pneumococcal polysaccharide vaccine (PPV-23) are available in China, the costs are borne by the consumer, resulting in low coverage for PCV-7. We aimed to conduct a simulation study to assess the cost-effectiveness and health benefits of PCV-7, 13-valent pneumococcal conjugate vaccine (PCV-13) and PPV-23 to prevent childhood pneumonia and other vaccine-preventive diseases in China. METHODS: An economic evaluation was performed using a Markov simulation model. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from previous studies. A hypothetical cohort of 100,000 newborns (focusing on pneumococcal diseases ≤7 years old) was followed up until death or 100 years of age. The model incorporated the impact of vaccination on reduction of incidence of pneumococcal diseases and mortality of children ≤7 years. Outcomes are presented in terms of disease cases averted, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. RESULTS: Under baseline assumptions, PPV-23 is currently the only cost-effective option, whereas PCV-13 showed the greatest impact on pneumococcal disease burden, reducing invasive pneumococcal diseases by 31.3%, pneumonia by 15.3% and gaining 73.8 QALYs (10,000 individuals at discount rate of 3%). Incremental cost-effectiveness ratios of PCV-13 and PCV-7 are US$29,460/QALY and US$104,094/QALY, respectively, showing no cost-effectiveness based on the World Health Organization recommended willingness-to-pay threshold. On the other hand, the incremental cost-effectiveness ratios of PCVs were most sensitive to vaccination costs; if it reduces 4.7% and 32.2% for PCV-7 and PCV-13, respectively, the vaccination will be cost-effective. CONCLUSIONS: To scale up current vaccination strategies and achieve potential health benefits, the replacement of PCV-7 with PCV-13 should be considered. As well, PCV's costs need to be reduced by increasing public subsidies and providing financial support to poor families.

Do different parenting patterns impact the health and physical growth of 'left-behind' preschool-aged children? A cross-sectional study in rural China.

BACKGROUND: Many migrants from rural China seek work in urban areas and leave their children in their home villages to be raised by relatives. These children are often referred to as 'left-behind children'. Parental migration tends to have a profound impact on a child's growth. This study sought to assess the prevalence of illness and malnutrition among children in rural areas raised with different parenting patterns and to explore factors affecting their health and development. METHOD: A cross-sectional survey was conducted to examine the physical health of children raised with different parenting patterns and to explore associated risk factors. In total, this study examined 735 children ages 3-6 years in eight rural villages in two counties of Shandong Province. Their primary caregivers were interviewed with a semi-structured questionnaire. Anthropometric measurements of the children were taken and their nutritional status was determined according to WHO Child Growth Standards. RESULTS: This study found a relatively high prevalence of wasting, overweight and obesity among left-behind children. After potential confounders were controlled for, the parenting pattern, annual household income and health literacy of the primary caregiver significantly influenced the health and developmental indicators of children. CONCLUSIONS: This study highlighted the impact of the characteristics of the primary caregiver on a child's health and development and the importance of practical interventions for preschool-aged children who are left behind and raised with different parenting patterns.

Developmental Origins of Health and Disease (DOHaD): Implications for health and nutritional issues among rural children in China.

In China, with fast economic growth, health and nutrition status among the rural population has shown significant improvement in the past decades. On the other hand, burden of non-communicable diseases and prevalence of related risk factors such as overweight and obesity has also increased. Among rural children, the double burden of malnutrition and emerging overweight and obesity has been neglected so far. According to the theory of Developmental Origin of Health and Diseases (DOHaD), malnutrition, including both undernutrition (stunting and wasting) and over-nutrition (overweight and obesity) during childhood is closely related to worsened health outcomes during adulthood. Such a neglected problem is attributable to a complicated synergy of social and environmental factors such as parental migration, financial situation of the household, child-rearing knowledge and practices of the primary caregivers, and has implications for public health. Based on literature review of lessons from the field, intervention to address malnutrition among rural children should be a comprehensive package, with consideration of their developmental environment and geographical and socioeconomic diversity. The scientific evidence on DOHaD indicates the probability and necessity of prevention of adult disease by promotion of maternal and child health and reducing malnutrition by provision of high-quality complementary foods, promotion of a well-balanced dietary pattern, and promotion of health literacy in the public would bring a potential benefit to reduce potential risk of diseases.

Amniotic Fluid Embolism (AFE) in China: Are maternal mortality and morbidity preventable?

A case of hospital-patient conflict has occurred in China that has lifted billows in the public and highlighted the lethality of amniotic fluid embolism (AFE). AFE is a rare but severe obstetric complication with high maternal mortality and morbidity. Globally, the incidence of AFE is estimated to be approximately 2 to 6 per 100,000 deliveries. The maternal mortality rate (MMR) attributable to AFE ranges between 0.5 to 1.7 deaths per 100,000 deliveries in the developed world and 1.9 to 5.9 deaths per 100,000 deliveries in the developing world. In developed countries, AFE often accounts for a leading cause of maternal mortality; whereas the proportion of maternal death caused by AFE tends to be not as dominant compared to common perinatal complications in developing countries. With the mechanism remaining to be elucidated, AFE can neither be predicted nor prevented even in developed countries. Treatment requires a set of highly intensive advanced emergency obstetric care, challenging obstetric care in developing countries. Although this complication is currently far from preventable, China has potential to improve the prognosis of AFE by strengthening the emergency obstetric care system.

Comparison of the middle-aged and older users' adoption of mobile health services in China.

OBJECTIVE: Given the increasing number of older people, China has become an aging society. A mobile health service is a type of health informatics that provides personalized healthcare advice to those who require it, especially the older people and the middle-aged. However, few studies consider the adoption of mobile health services with regard to older and middle-aged users. This paper explored a research model based on the value attitude behavior model, theory of planned behavior, and four aging characteristic constructs to investigate how older and middle-aged citizens adopted mobile health services. METHOD: The hypothesized model was empirically tested using data collected from a survey of 424 residents older than 40 years in China. Structural equation modeling was used to estimate the significance of the path coefficients. RESULTS: The findings revealed that (1) perceived value, attitude, perceived behavior control, and resistance to change can be used to predict intention to use mobile health services for the middle-aged group; (2) perceived value, attitude, perceived behavior control, technology anxiety, and self-actualization need positively affected the behavior intention of older users; and (3) subjective norm and perceived physical condition showed no significant effects on the behavior intention to use mobile health services for the two groups. The theoretical and practical implications and contributions of this study are then discussed.