Characteristics of subjects with type 2 diabetes enrolled in randomized controlled trials and non-randomized controlled trials in Japan: A systematic review.

AIMS/INTRODUCTION: This study aimed to understand the characteristics of type 2 diabetes subjects enrolled in randomized controlled trials (RCTs) and non-RCTs according to therapeutic regimens through systematic literature review. MATERIALS AND METHODS: PubMed and the database of the Japanese Medical Abstract Society (ICHUSHI) were searched for studies published from 2010 to 2019 reporting the efficacy and safety of glucose-lowering drugs in Japanese individuals with suboptimally controlled type 2 diabetes, and therapeutic regimens, demographics and clinical characteristics at the baseline were extracted. We evaluated the treatment arms, not the placebo arms. RESULTS: The literature searches identified 2,656 publications, 145 of which met all eligibility criteria and included 282 eligible arms. In the past 10 years, dipeptidyl peptidase-4 inhibitor was the most frequently studied in both RCTs and non-RCTs. Regarding the characteristics of enrolled subjects, sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist have been studied more in relatively obese subjects, and insulin has been studied in higher proportion of subjects with disease duration ≥10 years. Most of the RCTs included subjects aged 55-64 years, whereas a higher proportion of dipeptidyl peptidase-4 inhibitor and insulin arms in the non-RCTs included those aged ≥65 years. Dipeptidyl peptidase-4 inhibitor and sodium-glucose cotransporter 2 inhibitor were evaluated in subjects with no abnormalities in blood pressure or lipid parameters; however, only a few reports of those parameters have been assessed with glucagon-like peptide-1 receptor agonist and insulin. CONCLUSIONS: As RCTs and non-RCTs differ in the baseline characteristics of type 2 diabetes subjects, it is necessary to integrate and evaluate both to understand the actual treatment status of type 2 diabetes.

Cost-effectiveness analysis of dupilumab among patients with oral corticosteroid-dependent uncontrolled severe asthma in Japan.

BACKGROUND: Asthma is a common, chronic inflammatory airway disorder, with up to 1,177,000 people receiving asthma treatment in Japan. Dupilumab is a first-in-class, monoclonal antibody for the treatment of atopic diseases, including persistent asthma. The objective of this study was to assess the cost-effectiveness of dupilumab, compared with other biologics, as add-on treatment to background therapy in patients aged ≥12 years with uncontrolled, persistent asthma in Japan. METHODS: A life-time Markov cohort model was used to conduct cost-effectiveness analysis from the Japanese healthcare payer perspective with an annual discount rate of 2%. Dupilumab was compared with benralizumab and mepolizumab, and against omalizumab (as a hypothetical scenario). Inputs were informed by dupilumab clinical trials (VENTURE [NCT02528214] and QUEST [NCT02414854] trials), the literature, official Japanese sources and expert opinions. RESULTS: The base case results suggest that treatment with dupilumab leads to fewer severe exacerbations and increased life-years (LYs) and quality-adjusted LYs (QALYs) than benralizumab and mepolizumab. At a willingness-to-pay (WTP) threshold of ¥5,000,000 per QALY gained, dupilumab was the dominant strategy (lower cost, increased QALYs) versus benralizumab, and cost-effective versus mepolizumab with an incremental cost-effectiveness ratio (ICER) of ¥1,010,921 (US$9,190, US$1 = ¥110). Versus omalizumab, dupilumab was not cost-effective (ICER of ¥10,802,368 [US$98,203]). CONCLUSIONS: In Japan, dupilumab, as an add-on to background therapy, is economically dominant compared with benralizumab, and cost-effective versus mepolizumab.

[SURVEY OF PATIENTS' PERSPECTIVE ON SURGERY FOR CHRONIC RHINOSINUSITIS WITH NASAL POLYPS].

OBJECTIVE: To ensure that the best possible information is available for selecting treatment options in patients who have chronic rhinosinusitis with nasal polyps (CRSwNP), it is necessary to assess experiences with surgical procedures in real-world clinical practice. METHODS: We used an internet questionnaire to survey 300 patients who had a history of CRSwNP surgery or had been recommended for such surgery. RESULTS: The patients who underwent surgery showed high satisfaction with the effectiveness of the surgery. However between 20% and 30% were notably dissatisfied with the safety of the procedure, its effects on quality of life (QOL), its economic impact, and its influence on societal activities, such as attendance at work or school. This dissatisfaction tended to be particularly pronounced among older patients and those who had multiple surgeries. The primary reasons given for avoiding surgery were "afraid of surgery," "no time for hospitalization and treatment," and "surgery is too expensive." CONCLUSION: Our research indicates that, although recipient patients are highly satisfied with the effectiveness of surgery for CRSwNP, a number of patients hesitate because of concerns about safety, cost, and societal activities such as work and school attendance. These findings suggest that treatment in a clinical setting should consider not only therapeutic effects but also the patient's attitude and situation.

Real-world treatment and health care resource use among severe asthma patients in Japan.

BACKGROUND: There are limited studies on healthcare resource use (HCRU) among adult asthma patients in Japan using real-world evidence, and analysis on acute treatment and associated costs stratified by disease severity is further limited. This study aimed to characterize the disease burden of severe asthma patients in Japan in terms of HCRU and comorbid medical conditions, with particular interest in oral corticosteroid (OCS) dependency. METHODS: This retrospective cohort study of asthma patients used data from a claims database of diagnosis procedure combination hospitals in Japan. The severe asthma cohort included patients treated with OCS for more than 180 days in one year before the index date, with at least one asthma diagnosis claim. Comorbidity and drug use in the look-back period, HCRU, assumed OCS-related adverse events, and asthma exacerbations in the follow-up period were analyzed. RESULTS: Costs associated with the treatment of severe asthma were approximately twice that of mild/moderate asthma, and the annual median cost of patients hospitalized due to asthma reached ¥448,000 (USD $4073). Annual asthma exacerbation rate was higher in the severe asthma cohort than in the mild/moderate cohort. Patients with longer OCS use in the previous year had higher risks of secondary adrenal insufficiency, osteoporosis, and pneumonia in the following year. CONCLUSIONS: OCS use among asthma patients in Japan incurred greater medical and economic burden. Better understanding of the disease characteristics including the severity of asthma and appropriate management of disease burden will lead to more optimal use of healthcare resources in Japan.

Patient and physician preferences for atopic dermatitis injection treatments in Japan.

Background: Recently, biologic agents administered as a subcutaneous injection have been introduced as treatment options for atopic dermatitis (AD). Biologic treatments differ considerably from traditional topical and systemic anti-inflammatory treatments, and it is unclear how this may impact patient and physician preferences for treatments.Objective: To examine the treatment preferences for new injection treatments of patients and physicians.Methods: Discrete choice experiment methodology was used to quantify preferences for treatments via an online survey. Participants were presented with a series of choice scenarios; treatment options were described using the following attributes: add-on or replacement treatment, efficacy of improving rashes and itching, time until response, place of administration, injection site reaction, risk of mild-to-moderate and severe side effects, frequency of administration and cost.Results: 76.67% of physicians and 46.24% of patients opted-in to the new treatment in the scenarios presented. Of those who opted-in to treatment, physicians were more likely to value the efficacy of treating rashes and were more concerned about cost than patients. Patients preferred add-on treatments and were against self-administering the treatment at home.Conclusion: Overall patients and physicians differ in their preferences for AD treatments. These findings have implications for shared decision making and clinical practice.

Health-care resource use and current treatment of adult atopic dermatitis patients in Japan: A retrospective claims database analysis.

The real-world evidence on the profiles of patients suffering from atopic dermatitis (AD) in Japan is sparse. A retrospective claim database analysis was conducted to estimate the health-care resource use (HCRU) and current AD treatment. Data from October 2013 to September 2016 were extracted from the JMDC (Tokyo, Japan) claims database. HCRU was assessed by a comparison of AD patients and matched non-AD controls. A multivariate analysis was performed to estimate HCRU attributable to AD. AD patients (n = 39 893) have more claims of certain diagnoses such as rhinitis, viral and fungal infections, sleep disorders and conjunctivitis as well as higher HCRU (outpatient visits, prescriptions of AD-related and non-AD-related medications, phototherapy, laboratory tests) than matched non-AD controls (n = 39 893). Treatment pattern analysis included treatment-naive patients (n = 8478) and previously treated AD patients (n = 30 109). Approximately 20% of previously treated patients were on the continuous systemic treatment during 18-month follow up. Systemic corticosteroids were the most frequently used systemic treatments. Oral cyclosporin was less frequently used in both groups, but for the longest duration. Almost half of previously treated patients with oral cyclosporin continued treatment for more than 3 months. In conclusion, HCRU was higher in AD patients than non-AD controls, indicating a high burden of the disease imposed on AD patients. Continuous administration of systemic treatment, such as oral cyclosporin, systemic corticosteroids and phototherapy, observed in AD patients sheds light on the difficulties of managing AD in Japanese clinical practise.

Disease burden of fractures among patients with osteoporosis in Japan: health-related quality of life, work productivity and activity impairment, healthcare resource utilization, and economic costs.

Osteoporosis remains undertreated in Japan, and bone fractures are the most frequent complications imposing heavy burden on individuals and the community. This paper investigates the clinical and economic burden of fractures among osteoporosis patients in Japan. The Japan National Health and Wellness Survey 2012-2014 database was used for analysis. Respondents aged ≥ 50 years and indicated a physician diagnosis of osteoporosis (N = 1107) were categorized into three subgroups: no prior fracture (N = 693), single fracture (N = 242), and multiple (≥ 2) fractures (N = 172). Health-related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization and associated direct and indirect costs were compared across three fracture subgroups adjusting for respondents' sociodemographic and clinical characteristics using generalized linear regression models. The estimated fracture prevalence among respondents with osteoporosis who were ≥ 50 years was 37.4%, of whom 41.5% had multiple fractures. Relative to osteoporosis respondents with no fracture and with single fracture, those with multiple fractures reported significant higher disability in HRQoL, more healthcare resource utilization, and were associated with higher direct costs. Improved treatment of fractures among osteoporosis patients is necessary and may help reduce the clinical and economic burden in this osteoporosis population.

Treatment costs and cost drivers among osteoporotic fracture patients in Japan: a retrospective database analysis.

This study estimated the direct medical costs of osteoporotic fractures from a large claim database in Japan. We further identified several comorbidities which drove the treatment costs. The results would contribute to health economic analysis as well as understanding of individual financial burden in Japan. INTRODUCTION: The purposes of this study were to estimate treatment costs of osteoporotic fractures and to investigate the cost drivers. METHODS: Male and female patients aged 50 years and older with a hip, vertebral, or non-hip/non-vert (NHNV) fracture between April 2008 and December 2016 were analyzed from claim database. Two types of costs were estimated. The incremental yearly costs of fractures and comorbidity treatments (total medical costs) were calculated by subtracting pre-fracture costs from post-fracture costs. The costs exclusive for fracture treatments (fracture treatment costs) were estimated by summing up the costs of fracture treatments within 1 year after fracture. The associations between comorbidities and costs were examined with a generalized linear model. RESULTS: Total 12,898 patients were identified (83% was female). The total medical costs of fractures were $14,592 for male-hip, $15,691 for female-hip, $4268 for male-vertebral, $3819 for female-vertebral, $3790 for male-NHNV, and $4259 for female-NHNV. The fracture treatment costs were $4506 for male-hip, $5427 for female-hip, $1022 for male-vertebral, $1044 for female-vertebral, $1035 for male-NHNV, and $1408 for female NHNV. Three comorbidities were associated with increasing fracture treatment costs whereas four comorbidities were associated with decreasing fracture treatment costs. Five comorbidities were associated with increasing total medical costs whereas one comorbidity was associated with decreasing total medical costs. CONCLUSIONS: Yearly treatment costs were increased considerably after fracture. Several comorbidities were considered to be cost drivers for osteoporotic fracture treatment. The cost estimates with different patient profile would support conducting health economic analysis in the future.

[Considerations of screening and brief intervention among high-risk drinkers in Japan: from the perspectives of feasibility and cost-effectiveness].

One of the alcohol-related goals in Japan's health promotion campaign called Health Japan 21 (secondary term) is to reduce the number of high-risk drinkers (20 years old or above) who consume 40g or more pure alcohol/day in men and 20g or more in women by year 2022. To achieve this goal, a further expansion of screening and brief intervention (SBI) in the medical setting is essential. In this research, realistic and cost-effective SBI scenarios in Japan were investigated based on international systematic review and clinicians' opinions from a semi-structured interview. Several SBI scenarios were built with 2 levels of intervention based on the AUDIT scores of 8-15 (brief advice) and 16-19 (brief advice and counseling, continuous intervention), and a simulation was conducted by applying different probabilities and success rates into the scenarios. Information associated with preparation and implementation of SBI at the 2 levels was also estimated and annual costs of SBI per drinker were calculated. It was found that approximately 2,390,000 and 530,000 high-risk drinkers require brief and extensive interventions, respectively. Furthermore, incremental costs per quality-adjusted life year (QALY) gained were calculated at 723,415 yen for brief intervention and 944,762 yen for extensive intervention, suggesting cost-effectiveness of SBI in Japan. Given the limited national healthcare budget and operational challenges such as time to provide SBI especially in the primary care setting in Japan, roles of healthcare providers and wider use of information technology were discussed with some suggestions. Furthermore, lighter and more frequent interventions at various levels and not only at the medical setting but also at multiple social settings (such as workplace and among family and friends) were discussed to increase the cost-effectiveness of SBI and to keep the number of high-risk drinkers who have successfully reduced their alcohol consumption.

Estimating the economic effects of reduced drinking in Japan based on the methodologies of cost-of-illness studies on alcohol in Japan and overseas.

One of the alcohol-related goals in Japan's health promotion campaign called Health Japan 21 (secondary term) is to reduce the number of high-risk drinkers (20 years old or above) who consume 40g or more pure alcohol/day in men and 20g or more in women by year 2022. To achieve this goal, it is important for both the government and clinicians to understand the cost-of-illness associated with harmful drinking in Japan and .effectively reflect it into related poli- cies. In this study, direct and indirect costs attributable to alcohol based on conventional cost-of-illness study methodologies were estimated to be approximately 9.9 trillion yen using 2012 data. Furthermore, economic effects brought by achieving the goal of Health Japan 21 (seconda'ry term) were further analyzed by incorporating parameters such as employment rates, drinking volume and frequency by age group and gender. The authors.had previously estimated possible savings of as much as 381.3 billion yen, before subtracting associated intervention costs and decreased tax revenue from purchasing alcohol beverages. The scenario analysis in this study provided lower savings of approximately 158.4-194.6 billion yen. However, the estimates excluded high-risk drinkers in their 20s, early 30s and over 70, who account for a good part of high-risk drinkers in Japan. Furthermore, considerations of employment rates and average annual salaries into the calculations of economic loss due to premature mortality tend to ignore productivity loss (absenteeism and presentism) of high-risk drinkers and opportunity costs of home-makers or care-givers. Thus, possibly underestimated 158.4 billion yen was considered as realistic as possibly overestimated 381.3 billion yen. Despite such variations, economic effects brought by achieving reduced drinking among high-risk drinkers seemed to support related policies and disease management in Japan.

Awareness and treatment of alcohol dependence in Japan: results from internet-based surveys in persons, family, physicians and society.

AIMS: To understand current awareness of, and views on, treatment of alcohol dependence in Japan. METHODS: (a) Nationwide internet-based survey of 520 individuals, consisting of 52 diagnosed alcohol-dependent (AD) persons, 154 potentially alcohol-dependent (ADP) persons, 104 family members and 106 friends/colleagues of AD persons, and 104 general individuals, derived from a consumer panel where the response rate was 64.3%. We enquired into awareness about the treatment of alcohol dependence and patient pathways through the healthcare network. (b) Nationwide internet-based survey of physicians (response rate 10.1% (2395/23,695) to ask 200 physicians about their management of alcohol use disorders). RESULTS: We deduced that 10% of alcohol-dependent Japanese persons had ever been diagnosed with alcohol dependence, with only 3% ever treated. Regarding putative treatment goals, 20-25% of the AD and ADP persons would prefer to attempt to abstain, while 60-75% preferred 'reduced drinking.' A half of the responding physicians considered abstinence as the primary treatment goal in alcohol dependence, while 76% considered reduced drinking as an acceptable goal. CONCLUSION: AD and ADP persons in Japan have low 'disease awareness' defined as 'understanding of signs, symptoms and consequences of alcohol use disorders,' which is in line with the overseas situation. The Japanese drinking culture and stigma toward alcohol dependence may contribute to such low disease awareness and current challenging treatment environment. While abstinence remains the preferred treatment goal among physicians, reduced drinking seems to be an acceptable alternative treatment goal to many persons and physicians in Japan.