The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan.

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023-August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios.

A quantitative cross-sectional study of the burden of caring for patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex-associated epilepsy in Japan.

INTRODUCTION: Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC)-associated epilepsy are rare conditions associated with severe childhood-onset epilepsy. Caregivers play a critical role in the patients' care and may experience significant psychosocial and socioeconomic burden. This cross-sectional study determined the burden of caring for patients with these rare epilepsy conditions in Japan. METHODS: A quantitative online survey was used to assess patients' and caregivers' characteristics and the caregivers' emotional state, among others. Several validated questionnaires were used: the Hospital Anxiety and Depression Scale (HADS; 0-21 score) assessed the caregivers' emotional wellbeing, the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM; 0-100 score) assessed the health-related quality of life (HRQoL) of the caregivers and their families, and the Work Productivity and Activity Impairment General Health (WPAI:GH; 0-100 % score) questionnaire assessed work productivity. RESULTS: A total of 36 caregivers responded (median [interquartile range (IQR)] age 43.5 [39.5, 48.3] years; 33/36 [92 %] female; 13/36 [36 %] working part-time and 13/36 [36 %] not working). Participants cared for 7/36 (19 %), 19/36 (53 %), and 10/36 (28 %) patients with LGS, DS, and TSC, respectively (median [IQR] age, 11.0 [6.8, 16.3] years; age at first seizure, 0 [0, 0] years). Patients received a median (IQR) of 4 (3, 5) treatment drug types. Patients experienced median (IQR) 3.0 (0, 21.0) epileptic seizures in the previous week; 28/36 (78 %) had severe intellectual disabilities, and 34/36 (94 %) had developmental delays. Caregivers reported stress (17/36 [47 %]), sleep problems (13/36 [36 %]), and anxiety (12/36 [33 %]). They spent a median (IQR) of 50.0 (17.5, 70.0) hours caregiving in the previous week, with 3.0 (1.0, 11.0) hours of seizure-specific care. Caregivers reported that their lives would be easier with a median (IQR) of 1.5 (0, 5.0) hours fewer per week caring for patients during/following seizures. Median HADS scores were 9.5 ('suspected anxiety diagnosis') and 7.5 ('no depression') for caregivers, and PedsQL FIM Total median score was 60.1, indicating HRQoL impairment for the caregiver and their family. WPAI:GH scores for paid workers indicated important work impairment. Higher caregiving hours (≥ 21 h vs. < 21 h in the previous week) resulted in higher caregiver burden as indicated by the HADS Total score (p = 0.0062) and PedsQL FIM Total score (p = 0.0007). CONCLUSIONS: Caregivers of patients with LGS, DS, or TSC in Japan experience a significant time burden, reduced HRQoL, and high level of work/activity impairment. Caregivers provide round-the-clock care to patients and rely on family and specialized caring services to help manage the increased caregiving time, which tends to be associated with greater emotional burden and HRQoL impact.

Reduction in all-cause medical and caregiving costs through innovative health awareness projects in a rural area in Japan: a retrospective cohort study.

BACKGROUND: This study evaluates cost reduction in participants of a health awareness program (the Center of Healthy Aging Program, CHAP) in a Japanese rural area, characterized by an annual check-up and personalized interview on health issues and related risks immediately after the check-up. METHODS: This is a cross-sectional study using medical and caregiving costs and Japan-specific health check-up results in Hirosaki residents stored by the local government, which were individually-based linked to the CHAP information collected by Hirosaki University. This is the first study that used anonymized data with individually-based linkages to both a research institute and a local government in Japan under a strict limitation regarding linking to third-party data. We included residents who had been continuously enrolled for > 6 months as of 1 July 2015. We compared 5-year all-cause costs between three groups (with CHAP, with Japan-specific health check-up, and no check-up) using a multivariate negative binomial regression model considering risk factors including lifestyle habits and an inverse probability weight to adjust for baseline characteristics: age, sex, Charlson comorbidity index, baseline care level, and risk score of coronary heart diseases. RESULTS: A total of 384, 9805, and 32,630 residents aged 40-74 years were included for the CHAP, Japan-specific health check-up, and no check-up groups, respectively. The Japan-specific health check-up group showed older and higher Charlson comorbidity index than the others. After inverse probability weight adjusting, the amount of all-cause medical costs was significantly lower only in the CHAP group. Faster walking speed and exercise habits were independently associated with lower all-cause medical and caregiving costs. CONCLUSIONS: We demonstrated a 5-year all-cause cost reduction in residents who participated in the CHAP and also suggested the effect of exercise habits in Hirosaki, which indicated the significance of individually-based data linkages to external third-party data for all local governments to improve the health condition of residents.

Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 vaccine.

BACKGROUND: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a monovalent XBB.1.5 variant-adapted Fall 2023 COVID-19 vaccine (modified version: XBB monovalent) for adults aged ≥18 years on these outcomes. METHODS: A previously developed Susceptible-Exposed-Infected-Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19-related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. RESULTS: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial VE against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. CONCLUSIONS: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19-related infections, hospitalizations, and deaths.

The potential public health impact of the respiratory syncytial virus prefusion F protein vaccine in people aged ≥60 years in Japan: results of a Markov model analysis.

BACKGROUND: Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population. RESEARCH DESIGN AND METHODS: A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%. RESULTS: Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths. CONCLUSIONS: RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

Respiratory syncytial virus (RSV) is one of the most frequent disease-causing agents that leads to common cold symptoms. In older adults, infection with RSV can result in severe complications including bronchitis/bronchiolitis, lung infection (pneumonia) and in rare cases death. Older people and people with chronic heart or lung disease are more likely to experience complications. We estimated that more than 5 million RSV cases occur in older adults (≥60 years) over a three-year period (1.8 million over one year). Many older adults (≥60 years) will see their treating physician because of an acute RSV infection or will be hospitalized.Recently, a vaccine has been registered which protects older adults against RSV disease: the RSV prefusion F protein Older Adult (RSVPreF3 OA) vaccine. Vaccination with RSVPreF3 OA could prevent RSV infection in the older adult population and reduce the number of outpatient visits and hospitalizations; the impact is particularly high in Japan, where 35% of people are 60 years or older. We used a public health impact model to estimate how many RSV cases, hospitalizations and deaths could be prevented if 50% of people aged ≥ 60 years received the RSVPreF3 OA vaccine: We found that the vaccine could prevent about 1 million RSV infections, more than 728,000 outpatient visits, approximately 143,000 hospitalizations and 6,840 RSV-related deaths over a three-year period.Adding RSVPreF3 OA vaccine to the national immunization program in Japan could protect older adults against RSV disease and reduce the burden on patients and the healthcare system.

Cost-effectiveness of surveillance intervals after curative resection of colorectal cancer.

BACKGROUND: Major guidelines consistently recommend 5 years of postoperative surveillance for patients with colorectal cancer. However, they differ in their recommendations for examination intervals and whether they should vary according to disease stage. Furthermore, there are no reports on the cost-effectiveness of the different surveillance schedules. The objective of this study is to identify the most cost-effective surveillance intervals after curative resection of colorectal cancer. METHODS: A total of 3701 patients who underwent curative surgery for colorectal cancer at the National Cancer Center Hospital were included. A cost-effectiveness analysis was conducted for the five surveillance strategies with reference to the guidelines. Expected medical costs and quality-adjusted life years after colorectal cancer resection were calculated using a state-transition model by Monte Carlo simulation. The incremental cost-effectiveness ratio per quality-adjusted life years gained was calculated for each strategy, with a maximum acceptable value of 43 500-52 200 USD (5-6 million JPY). RESULTS: Stages I, II and III included 1316, 1082 and 1303 patients, respectively, with 45, 140 and 338 relapsed cases. For patients with stage I disease, strategy 4 (incremental cost-effectiveness ratio $26 555/quality-adjusted life year) was considered to be the most cost-effective, while strategies 3 ($83 071/quality-adjusted life year) and 2 ($289 642/quality-adjusted life year) exceeded the threshold value. In stages II and III, the incremental cost-effectiveness ratio for strategy 3 was the most cost-effective option, with an incremental cost-effectiveness ratio of $18 358-22 230/quality-adjusted life year. CONCLUSIONS: In stage I, the cost-effectiveness of intensive surveillance is very poor and strategy 4 is the most cost-effective. Strategy 3 is the most cost-effective in stages II and III.

Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age.

OBJECTIVE: Current guidelines recommend long-term image-based surveillance for patients with low-risk intraductal papillary mucinous neoplasms (IPMNs). This simulation study aimed to examine the comparative cost-effectiveness of continued versus discontinued surveillance at different ages and define the optimal age to stop surveillance. DESIGN: We constructed a Markov model with a lifetime horizon to simulate the clinical course of patients with IPMNs receiving imaging-based surveillance. We calculated incremental cost-effectiveness ratios (ICERs) for continued versus discontinued surveillance at different ages to stop surveillance, stratified by sex and IPMN types (branch-duct vs mixed-type). We determined the optimal age to stop surveillance as the lowest age at which the ICER exceeded the willingness-to-pay threshold of US$100 000 per quality-adjusted life year. To estimate model parameters, we used a clinical cohort of 3000 patients with IPMNs and a national database including 40 166 patients with pancreatic cancer receiving pancreatectomy as well as published data. RESULTS: In male patients, the optimal age to stop surveillance was 76-78 years irrespective of the IPMN types, compared with 70, 73, 81, and 84 years for female patients with branch-duct IPMNs <20 mm, =20-29 mm, ≥30 mm and mixed-type IPMNs, respectively. The suggested ages became younger according to an increasing level of comorbidities. In cases with high comorbidity burden, the ICERs were above the willingness-to-pay threshold irrespective of sex and the size of branch-duct IPMNs. CONCLUSIONS: The cost-effectiveness of long-term IPMN surveillance depended on sex, IPMN types, and comorbidity levels, suggesting the potential to personalise patient management from the health economic perspective.

Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Risk of hospitalized infections in older elderly patients with rheumatoid arthritis treated with tocilizumab or other biological/targeted synthetic disease-modifying antirheumatic drugs: Evaluation of data from a Japanese claims database.

OBJECTIVE: We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA). METHODS: We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups (<65, ≥65 and <75, and ≥75 years). RESULTS: Of 5506 patients, 2265 (41.1%) were <65 years, 1709 (31.0%) were 65-74 years, and 1532 (27.8%) were ≥75 years. Crude incidence rates (/100 person-years) of HIs were 3.99, 7.27, and 10.77, respectively. In the oldest group, aRRs (95% confidence interval) for HIs (b/tsDMARDs versus TCZ) were as follows: etanercept, 2.40 (1.24-4.61); adalimumab, 1.90 (0.75-4.83); golimumab, 1.21 (0.66-2.23); and abatacept, 0.89 (0.49-1.62). In the other age groups, the noticeable difference was a lower aRR of etanercept versus TCZ in the youngest group (0.30, 0.11-0.85). CONCLUSION: In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with DNA mismatch repair deficient (dMMR) tumors, third edition.

BACKGROUND: Clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. The accumulated evidence of tumor agnostic agent has been made since PD-1 inhibitor was approved and used in clinical practice. Therefore, we have revised the guideline "Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition". METHODS: Clinical questions regarding medical care were formulated for patients with dMMR advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO and the public comments among all societies' members were done. RESULTS: The current guideline describes two clinical questions and eight recommendations for whom, when, and how MMR status should be tested. CONCLUSION: In this guideline, the committee proposed eight recommendations for performing MMR testing properly to select patients who are likely to benefit from immunotherapy.

A systematic review of the characteristics of data assessment tools to measure medical doctors' work-related quality of life.

PURPOSE: Remarkable progress in healthcare technology has recently been made alongside changes in concepts related to drugs and medical devices. It is speculated that this progress benefits not only patients but also healthcare professionals, such as medical doctors. We performed a systematic review of the characteristics of current data assessment tools to measure medical doctors' work-related quality of life (QOL). METHODS: A literature search was conducted through PubMed and Ichushi-Web in 2020. The related search terms used were 'medical doctor,' 'quality of work life,' and 'questionnaire/interview.' Two reviewers independently screened the studies, and the characteristics of the QOL assessment tools used in the identified studies were qualitatively reviewed and summarized. RESULTS: In total, 5,443 and 760 articles were retrieved from PubMed and Ichushi-Web, respectively, of which 82 studies were included in this review. Sixty-five (79%) studies used structured questionnaires, and 17 (21%) studies used semistructured questionnaires. In terms of the study purpose, the identified studies mainly included four: mental health, the work or labor situation, satisfaction, and QOL. Components used to measure work-related QOL included satisfaction, burnout, QOL, the work environment, stress, mental health, work-life balance, and others. None of the studies used an originally developed QOL questionnaire to assess the work-related benefits of medical doctors. CONCLUSION: This systematic review found that there is a lack of studies directly assessing the work-related QOL of medical doctors and a lack of effective data collection tools to assess all work-related QOL components.

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with high tumor mutational burden tumors.

The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we developed recommendations for tumor-agnostic treatments in patients with solid tumors with DNA mismatch repair deficient or neurotrophic receptor tyrosine kinase fusions. Recently, immune checkpoint inhibitors have shown efficacy in patient with tumor mutation burden-high (TMB-H) solid tumors and have been established as a third tumor-agnostic agent, making it necessary to develop the guideline prioritized for these patients. Clinical questions regarding medical care were formulated for patients with TMB-H advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. The current guideline describes three clinical questions and seven recommendations for whom, when, and how TMB should be tested, and what is recommended for patients with TMB-H advanced solid tumors. In this guideline, the committee proposed seven recommendations for performing TMB testing properly to select patients who are likely to benefit from immunotherapy.

Factors associated with financial toxicity in patients with breast cancer in Japan: a comparison of patient and physician perspectives.

BACKGROUND: Financial toxicity (FT) is a notable concern for patients with breast cancer worldwide. The situation regarding FT in Japan, however, has not been well explored. This study examined FT in patients with breast cancer in Japan and presented an overview of the group study's overall findings. METHODS: The survey used the Questant application and primarily targeted patients with breast cancer attending research facilities and physicians who are members of the Japanese Breast Cancer Society. The Japanese version of the Comprehensive Score for FT (COST) was used to quantify patients' FT. Multiple regression analysis was used to identify factors related to FT in patients with breast cancer in Japan and evaluate the sufficiency of information support level (ISL) for medical expenses. RESULTS: We collected 1558 responses from patients and 825 from physicians. In terms of factors affecting FT, recent payments had the highest impact, followed by stage, and related departments positively affecting FT. Conversely, factors such as income, age, and family support were found to negatively affect FT. A significant discrepancy was identified between patients and physicians in perceived information support, with patients frequently feeling unsupported and physicians believing that they have provided adequate support. Furthermore, differences in the frequency of explanations and opportunities to ask questions about medical costs across FT grades were found. The analysis also showed that physicians with a better understanding of information support needs and greater knowledge of medical costs tended to provide more support that is comprehensive. CONCLUSION: This study emphasizes the importance of addressing FT in patients with breast cancer in Japan and highlights the need for enhanced information support, deeper understanding by physicians, and collaborative efforts among professionals to mitigate financial burden and provide personalized, tailored support for individual needs.

Preferences and values for government policies on infectious disease outbreaks and epidemics for the Japanese population: a conjoint analysis.

AIMS: To investigate the preferences of the Japanese population for government policies expected to address infectious disease outbreaks and epidemics. METHODS: We performed a conjoint analysis based on survey data in December 2022 (registration number: UMIN000049665). The attributes for the conjoint analysis were policies: tests, vaccines, therapeutic drugs, behavior restrictions (e.g. self-restraint or restrictions on the gathering or travel of individuals and the hours of operation or serving of alcoholic beverages in food/beverage establishments), and entry restrictions (from abroad), and monetary attribute: an increase in the consumption tax from the current 10%, to estimate the monetary value of the policies. A logistic regression model was used for the analysis. RESULTS: Data were collected from 2,185 respondents. The accessibility of tests, vaccines, and therapeutic drugs was preferred regardless of the accessibility level. The value for accessibility of drugs to anyone at any medical facility was estimated at 4.80% of a consumption tax rate, equivalent to JPY 10.5 trillion, which was the highest among the policies evaluated in this study. The values for implementing behavior or entry restrictions were negative or lower than those for tests, vaccines, and drugs. LIMITATIONS: Respondents chosen from an online panel were not necessarily representative of the Japanese population. Because the study was conducted in December 2022, a period during the coronavirus disease 2019 (COVID-19) pandemic, the results may reflect the situation at that time and potentially be subject to rapid change. CONCLUSIONS: Among the policy options evaluated in this study, the most preferred option was easily accessible therapeutic drugs and their monetary value was substantial. Wider accessibility of tests, vaccines, and drugs was preferred over behavior and entry restrictions. We believe that the results provide information for policymaking to prepare for future infectious disease epidemics and for assessing the response to COVID-19 in Japan.

Value elements and methods of value-based pricing for drugs in Japan: a systematic review.

INTRODUCTION: Value-based pricing (VBP) can be a promising tool for optimizing drug prices. However, there is no consensus on the specific value elements and pricing method that should be used for VBP. AREAS COVERED: We performed a systematic review and narrative synthesis to investigate the value elements and pricing method for VBP. The main inclusion criterion was that value elements, VBP method, and estimated prices for actual drugs were reported. We performed a search in MEDLINE and ICHUSHI Web. Eight articles met the selection criteria. Four studies adopted the cost-effectiveness analysis (CEA) approach and the others used different approaches. The CEA approach included the value elements of productivity, value of hope, real option value, disease severity, insurance value in addition to costs and quality-adjusted life years. The other approaches used efficacy, toxicity, novelty, rarity, research and development costs, prognosis, population health burden, unmet needs, and effectiveness. Each study used individual methods to quantify these broader value elements. EXPERT OPINION: Both conventional and broader value elements are used for VBP. To allow VBP to be widely applied to various diseases, a simple, versatile method is preferable. Further research is needed to establish VBP method which enables to incorporate broader values.

Prevalence of multimorbidity and its associations with hospitalisation or death in Japan 2014-2019: a retrospective cohort study using nationwide medical claims data in the middle-aged generation.

OBJECTIVE: To describe the prevalence of multimorbidity and its associations with clinical outcomes across age groups. DESIGN: Retrospective cohort study using nationwide medical claims data. SETTING: Carried out in Japan between April 2014 and March 2019. PARTICIPANTS: N=246 671 Japanese individuals aged 20-74 enrolled in the health insurance were included into the baseline data set for fiscal year (FY) 2014. Of those, N=181 959 individuals were included into the cohort data set spanning FY2014-FY2018. EXPOSURES: Multimorbidity was defined as having ≥2 of 15 chronic conditions according to the International Classification of Diseases 10th Revision codes of the Charlson Comorbidity Index. PRIMARY AND SECONDARY OUTCOMES: Primary outcome: the standardised prevalence of multimorbidity across age groups was evaluated using data from FY2014 and extrapolated to the Japanese total population. SECONDARY OUTCOME: hospitalisation or death events were traced by month using medical claims data and insurer enrolment data. Associations between multimorbidity and 5-year hospitalisation and/or death events across age groups were analysed using a Cox regression model. RESULTS: The standardised prevalence rate of multimorbidity in the nationwide Japanese total population was estimated to 26.1%. The prevalence rate with age was increased, approximately 5% (ages 20-29), 10% (30-39), 20% (40-49), 30% (50-59), 50% (60-69) and 60% (70-74). Compared with individuals aged 20-39 without multimorbidity, those with multimorbidity had a higher incidence of clinical events in any age group (HR=2.43 (95% CI 2.30 to 2.56) in ages 20-39, HR=2.55 (95% CI 2.47 to 2.63) in ages 40-59 and HR=3.41 (95% CI 3.23 to 3.53) in ages ≥60). The difference in the incidence of clinical events between multimorbidity and no multimorbidity was larger than that between age groups. CONCLUSIONS: Multimorbidity is already prevalent in the middle-aged generation and is associated with poor clinical outcomes. These findings underscore the significance of multimorbidity and highlight the urgent need for preventive intervention at the public healthcare level.

Predicting the Societal Value of Lecanemab in Early Alzheimer's Disease in Japan: A Patient-Level Simulation.

INTRODUCTION: Alzheimer's disease (AD), a neurodegenerative disorder that progresses from mild cognitive impairment (MCI) to dementia, is responsible for significant burden on caregivers and healthcare systems. In this study, data from the large phase III CLARITY AD trial were used to estimate the societal value of lecanemab plus standard of care (SoC) versus SoC alone against a range of willingness-to-pay (WTP) thresholds from a healthcare and societal perspective in Japan. METHODS: A disease simulation model was used to evaluate the impact of lecanemab on disease progression in early AD based on data from the phase III CLARITY AD trial and published literature. The model used a series of predictive risk equations based on clinical and biomarker data from the Alzheimer's Disease Neuroimaging Initiative and Assessment of Health Economics in Alzheimer's Disease II study. The model predicted key patient outcomes, including life years (LYs), quality-adjusted life years (QALYs), and total healthcare and informal costs of patients and caregivers. RESULTS: Over a lifetime horizon, patients treated with lecanemab plus SoC gained an additional 0.73 LYs compared with SoC alone (8.50 years vs. 7.77 years). Lecanemab, with an average treatment duration of 3.68 years, was found to be associated with a 0.91 increase in patient QALYs and a total increase of 0.96 when accounting for caregiver utility. The estimated value of lecanemab varied according to the WTP thresholds (JPY 5-15 million per QALY gained) and the perspective employed. From the narrow healthcare payer's perspective, it ranged from JPY 1,331,305 to JPY 3,939,399. From the broader healthcare payer's perspective, it ranged from JPY 1,636,827 to JPY 4,249,702, while from the societal perspective, it ranged from JPY 1,938,740 to JPY 4,675,818. CONCLUSION: The use of lecanemab plus SoC would improve health and humanistic outcomes with reduced economic burden for patients and caregivers with early AD in Japan.

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.

BACKGROUND: Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the 'Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)'. METHODS: Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. RESULTS: The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. CONCLUSION: The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.

In-Hospital Outcomes of Heart Failure Patients with Valvular Heart Disease: Insights from Real-World Claims Data.

Purpose: Heart failure (HF) is a serious public health burden that is rapidly increasing in the aging population. Valvular heart disease (VHD) is a known etiology of heart failure (HF); however, the impact of VHD on outcomes of patients with HF has not been well-studied in Japan. This study aimed to determine the rates of VHD in Japanese patients admitted for HF and explore associations of VHD with in-hospital outcomes through a claim-based analysis. Patients and methods: We analyzed claims data from 86,763 HF hospitalizations (January 2017 through December 2019) from the Medical Data Vision database. Common etiologies of HF were examined, then hospitalizations were categorized into those with VHD and those without. Covariate-adjusted models were used to explore the association of VHD with in-hospital mortality, length of stay, and medical cost. Results: Of 86,763 hospitalizations for HF, 13,183 had VHD and 73,580 did not. VHD was the second most frequent etiology of HF (15.2%). The most frequent type of VHD was mitral regurgitation (36.4% of all hospitalizations with VHD), followed by aortic stenosis (33.7%) and aortic regurgitation (16.4%). There was no significant difference in in-hospital mortality between hospitalizations with VHD vs those without (9.0% vs 8.9%; odds ratio [95% CI]: 1.01 [0.95-1.08]; p=0.723). Hospitalizations with VHD were associated with significantly longer length of stay (26.1 vs 24.8 days; incident rate ratio [95% CI]: 1.05 [1.03-1.07]; p<0.001) and higher medical costs (1536 vs 1195 thousand yen; rate ratio [95% CI]: 1.29 [1.25-1.32]; p<0.001). Conclusion: VHD was a frequent etiology of HF that was associated with significant medical resource use. Future studies are needed to investigate whether timely VHD treatment could reduce HF progression and its associated healthcare resource utilization.