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.

Cost-effectiveness of sodium-glucose cotransporter-2 inhibitors in the treatment of diabetic nephropathy in Japan.

AIM: To assess the cost-effectiveness of diabetic nephropathy treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors in Japanese clinical practice, considering diabetes-related complications. MATERIALS AND METHODS: A population-based Monte Carlo simulation was used to estimate the cost-effectiveness for people with diabetic nephropathy who initiated pharmacotherapy with an SGLT2 inhibitor plus conventional treatment or conventional treatment alone, based on quality-adjusted life-years (QALYs) and healthcare costs. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation study (CREDENCE) and the Japanese Society for Dialysis Research statistical survey were the primary sources of probability and mortality, while Japanese Health Insurance Claims Data were the cost source. The state transition model included diabetic nephropathy, hospitalization due to cardiovascular disease, dialysis, and death. One-way and probabilistic sensitivity analyses were used to explore model uncertainty. RESULTS: Using the threshold of JPY 5 000 000 per QALY, SGLT2 inhibitor plus conventional treatment was more cost-effective than conventional treatment alone, with an incremental cost-effectiveness ratio of JPY 654 309 per QALY. Treating 100 000 people, SGLT2 inhibitor plus conventional treatment prevented 2234 deaths and reduced 5793 fewer heart failure cases, 3967 fewer myocardial infarctions and stroke events. Sensitivity analysis affirmed the robustness of these results for patients aged under 70 years. CONCLUSIONS: The SGLT2 inhibitor treatment appeared to be cost-effective for the overall population of our study and particularly for younger patients (<70 years old). For older patients (≥70 years old), the cost-effectiveness was less clear and may require further evaluation. Decision-makers should consider this age-based heterogeneity when making recommendations about SGLT2 inhibitor treatment.

A Targeted Review of Worldwide Indirect Treatment Comparison Guidelines and Best Practices.

OBJECTIVES: Controls and governance over the methodology and reporting of indirect treatment comparisons (ITCs) have been introduced to minimize bias and ensure scientific credibility and transparency in healthcare decision making. The objective of this study was to highlight ITC techniques that are key to conducting objective and analytically sound analyses and to ascertain circumstantial suitability of ITCs as a source of comparative evidence for healthcare interventions. METHODS: Ovid MEDLINE was searched from January 2010 through August 2023 to identify publicly available ITC-related documents (ie, guidelines and best practices) in the English language. This was supplemented with hand searches of websites of various international organizations, regulatory agencies, and reimbursement agencies of Europe, North America, and Asia-Pacific. The jurisdiction-specific ITC methodology and reporting recommendations were reviewed. RESULTS: Sixty-eight guidelines from 10 authorities worldwide were included for synthesis. Many of the included guidelines were updated within the last 5 years and commonly cited the absence of direct comparative studies as primary justification for using ITCs. Most jurisdictions favored population-adjusted or anchored ITC techniques opposed to naive comparisons. Recommendations on the reporting and presentation of these ITCs varied across authorities; however, there was some overlap among the key elements. CONCLUSIONS: Given the challenges of conducting head-to-head randomized controlled trials, comparative data from ITCs offer valuable insights into clinical-effectiveness. As such, multiple ITC guidelines have emerged worldwide. According to the most recent versions of the guidelines, the suitability and subsequent acceptability of the ITC technique used depends on the data sources, available evidence, and magnitude of benefit/uncertainty.

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.

The emotional burden of caring for patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex-associated epilepsy: A qualitative study in Japan.

INTRODUCTION: Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are rare, childhood-onset conditions associated with severe, treatment-resistant epilepsy and developmental issues, including motor and cognitive impairment. Tuberous sclerosis complex (TSC) is a rare genetic disease commonly associated with epilepsy and other neuropsychiatric disorders. This cross-sectional, interview-based study examined the qualitative impact of caring for patients with LGS, DS, and TSC-associated epilepsy on caregivers in Japan, from the perspective of both caregivers and physicians. METHODS: The survey included a pre-interview worksheet to describe caregivers' emotional journeys, followed by a ≤ 60-minute one-on-one interview. Eligible participants were Japanese caregivers of patients with LGS, DS, or TSC treated for epilepsy symptoms, and Japan-residing pediatricians or neurologists treating ≥ 3 patients with LGS, DS, and/or TSC. Interview question responses were subjected to content analysis to identify the most common response tendencies and themes. RESULTS: Twenty-six caregivers responded (mean [standard deviation (SD)] age, 45.9 [9.5] years; age range 29-68; 92 % female), caring for patients with LGS (n = 5), DS (n = 10), and TSC (n = 11); patient mean (SD) age, 13.6 (10.0) years; age range 2-44; 27 % adults; 50 % female. Nineteen physicians, treating patients with LGS (n = 9), DS (n = 7), and TSC (n = 10), participated. Caregivers and physicians generally aligned on the factors affecting caregivers' emotional states / quality of life (QoL). The most frequently reported caregiver emotions at the time of diagnosis were shock and discouragement, anxiety for the future, and relief at receiving a diagnosis. Negative emotions throughout disease progression up until the time of survey were mainly caused by worsening of seizures, burden of constant caregiving / lack of free time, and patient's developmental issues. Positive emotions were linked to effective treatment / reduced seizures; more free time owing to the use of facilities, services, or other caregiving support; and developmental progress. Physicians acknowledged that caregivers required consultation services to support their emotional needs. In terms of unmet needs, caregiver and physician responses were aligned on the insufficient availability of services/facilities, the lack of effective treatments, and the uncertainties of adult patient care. CONCLUSIONS: Caregivers of patients with LGS, DS, or TSC-associated epilepsy in Japan reported a high degree of emotional burden related to frequent seizures, developmental issues, and constant caregiving. The burden of suboptimal treatment effectiveness, limited access to support services, and uncertainties in long-term care emphasize important unmet treatment needs.

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.

A randomized phase III study evaluating dexamethasone-based mouthwash to prevent chemotherapy-induced stomatitis in patients with breast cancer.

Stomatitis, which is a common side effect of chemotherapy, currently lacks a standardized approach for its prevention. Therefore, this multicenter, randomized, open-label, controlled phase III trial aims to assess the efficacy and safety of a dexamethasone-based mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. We will randomly assign 230 patients with early breast cancer scheduled to receive chemotherapy in a 1:1 ratio to either the dexamethasone-based mouthwash group (10 ml, 0.1 mg/ml; swish for 2 min and spit 4 times daily for 8 weeks) or the mouthwash-with-tap-water group. The incidence of stomatitis, measured using electronic patient-reported outcomes, is the primary endpoint.

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.

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.

[Health Economic Evaluation of Surgical Treatment for Cancer].

Conducting"health economic evaluation"is one of the most important issues for the efficient allocation of healthcare costs. Although the Central Social Insurance Medical Council in Japan(Chuikyo)introduced a cost-effectiveness evaluation system for drugs and medical devices in 2019, there are no reports of the system being officially utilized for medical procedures, including surgical treatments. Because it is often required to provide the best possible treatment to save lives, cancer care is an area where it is difficult to adapt"health economic evaluation". In addition, surgical treatment is more invasive than medical checkups or drug therapy, and complications and hospitalization costs vary widely from case to case, so the cooperation of the medical affairs department is essential in examining medical costs for health economic evaluation. Although QOL surveys are important for the evaluation of invasiveness, there are almost no large-scale studies that reflect the actual conditions of treatment, and none for Japanese and for patients undergoing cancer treatment. It is essential to conduct QOL surveys for future health economic evaluation. We will explain"health economic evaluation"of surgical treatment for cancer, using as examples the results of medical technology evaluation of surgical techniques that we have reviewed. In considering the"health economic evaluation"of surgical treatment for cancer, the medical cost and QOL surveys were considered to be particularly important. We look forward to future research.

Cost-Effectiveness of Vonoprazan Compared With Proton Pump Inhibitors in Patients Taking Low-Dose Aspirin for Secondary Prevention of Cardiovascular Events in Japan.

BACKGROUND: Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole. CONCLUSIONS: Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Three-year outcomes of robotic gastrectomy versus laparoscopic gastrectomy for the treatment of clinical stage I/II gastric cancer: a multi-institutional retrospective comparative study.

BACKGROUND: Oncological benefits of robotic gastrectomy (RG) remain unclear. We aimed to determine and compare the 3-year outcomes of RG and laparoscopic gastrectomy (LG) for the treatment of gastric cancer. METHODS: This was a multi-institutional retrospective study of patients who prospectively underwent RG in a previous study (UMIN000015388) and historical controls who underwent LG. Operable patients with cStage I/II primary gastric cancer were enrolled. The inverse probability of treatment weighting method based on propensity scores was used to balance patient demographic factors and surgeon volume between the RG and LG groups. The primary outcome measure was the 3-year overall survival rate (3yOS). RESULTS: Of the 1,127 patients in the previous study, 326 and 752 patients in the RG and LG groups, respectively, completed the study. The standardized difference of all confounding factors was reduced to 0.09 or less after weighting. In the weighted population, 3yOS was 96.3% and 89.6% in the RG and LG groups, respectively (hazard ratio [HR] 0.34 [0.15, 0.76]; p = 0.009), whereas there was no difference in 3-year recurrence-free survival rate (3yRFS) between the two groups (HR 0.58 [0.32, 1.05]; p = 0.073). Sub-analyses showed that RG improved 3yOS (HR 0.05 [0.01, 0.38]; p = 0.004) and 3yRFS (HR 0.05 [0.01, 0.34]; p = 0.003) in patients with pStage IA disease. Recurrence rates and patterns were similar between the RG and LG groups. RG did not improve the morbidity rate, however, it attenuated some of the adverse events, including anastomotic leakage and intra-abdominal abscess. RG improved estimated blood loss and duration of postoperative hospitalization. CONCLUSION: This study showed surgical and oncological safety of RG for cStage I/II gastric cancer considering the 3-year outcomes, compared with those of LG.

Association between financial toxicity and health-related quality of life of patients with gynecologic cancer.

OBJECTIVES: Patients often struggle with their financial situation during cancer treatment due to treatment-related costs or loss of income. This resulting negative effect is called financial toxicity, which is a known as a side effect of cancer care. This study aimed to evaluate the association between financial toxicity and health-related quality of life among patients with gynecologic cancer using validated questionnaires. METHODS: In this multicenter study, patients with gynecologic cancer receiving anti-cancer drug treatment for > 2 months were recruited. Patients answered the COmprehensive Score for Financial Toxicity (COST) tool, EORTC-QLQ-C30, disease-specific tools (EORTC-QLQ-OV28/CX24/EN24), and EQ-5D-5L. Spearman's rank correlation coefficient was used to determine associations. RESULTS: Between April 2019 and July 2021, 109 cancer patients completed the COST questionnaire. The mean COST score was 19.82. Strong associations were observed between financial difficulty (r = - 0.616) in the EORTC-QLQ-C30 and body image (r = 0.738) in the EORTC-QLQ-CX24, while weak associations were noted between the global health status/quality of life (r = 0.207), EQ-5D-5L index score (r = 0.252), and several function and symptom scale scores with the COST score. CONCLUSIONS: Greater financial toxicity was associated with worse health-related quality of life scores, such as financial difficulty in gynecologic cancer patients and body image in cervical cancer patients as strong associations, and weakly associated with general health-related quality of life scores and several function/symptom scales.

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.

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.

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.

Cost-effectiveness analysis of computer-aided detection systems for colonoscopy in Japan.

OBJECTIVES: The usefulness of computer-aided detection systems (CADe) for colonoscopy has been increasingly reported. In many countries, however, data on the cost-effectiveness of their use are lacking; consequently, CADe for colonoscopy has not been covered by health insurance. We aimed to evaluate the cost-effectiveness of colonoscopy using CADe in Japan. METHODS: We conducted a simulation model analysis using Japanese data to examine the cost-effectiveness of colonoscopy with and without CADe for a population aged 40-74 years who received colorectal cancer (CRC) screening with a fecal immunochemical test (FIT). The rates of receiving FIT screening and colonoscopy following a positive FIT were set as 40% and 70%, respectively. The sensitivities of FIT for advanced adenomas and CRC Dukes' A-D were 26.5% and 52.8-78.3%, respectively. CADe colonoscopy was judged to be cost-effective when its incremental cost-effectiveness ratio (ICER) was below JPY 5,000,000 per quality-adjusted life-years (QALYs) gained. RESULTS: Compared to conventional colonoscopy, CADe colonoscopy showed a higher QALY (20.4098 vs. 20.4088) and lower CRC incidence (2373 vs. 2415 per 100,000) and mortality (561 vs. 569 per 100,000). When the CADe cost was set at JPY 1000-6000, the ICER per QALY gained for CADe colonoscopy was lower than JPY 5,000,000 (JPY 796,328-4,971,274). The CADe cost threshold at which the ICER for CADe colonoscopy exceeded JPY 5,000,000 was JPY 6040. CONCLUSIONS: Computer-aided detection systems for colonoscopy has the potential to be cost-effective when the CADe cost is up to JPY 6000. These results suggest that the insurance reimbursement of CADe for colonoscopy is reasonable.

Cost-effectiveness analyses of biologic and targeted synthetic disease-modifying anti-rheumatic diseases in patients with rheumatoid arthritis: Three approaches with a cohort simulation and real-world data.

OBJECTIVE: To assess the cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. METHODS: We conducted three analyses: a lifetime analysis with a cohort model (Study A) and two short-term analyses (Studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and Study C evaluated costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database. RESULTS: In Study A, ICERs of all b/tsDMARDs were lower than 5.0 million Japanese yen (JPY) per QALY. In Study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (TCZ-SC; 1.9 million JPY) and SC abatacept (2.3 million JPY). In Study C, costs per person were lower for TCZ-SC (1.3 million JPY) and intravenous TCZ (1.6 million JPY) and effectiveness rates were higher for intravenous TCZ (45.3%) and infliximab (43.0%). CONCLUSION: The b/tsDMARDs with lower prices showed higher cost-effectiveness.

[Cost-Effectiveness Analysis and Budget Impact Analysis of Enzalutamide for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer].

We conducted cost-effectiveness analysis and budget impact analysis for androgen deprivation therapy (ADT) plus enzalutamide (ENZ) on patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the publicly-funded healthcare system perspective. Using a partitioned survival model, lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) of ADT＋ENZ were estimated against ADT alone, ADT plus abiraterone (ADT＋ABI), and ADT plus apalutamide (ADT＋APA). Total healthcare cost differences with and without ENZ in mHSPC therapy were estimated for the period from 2022 to 2026. Based on cost-effectiveness analysis, the ICER of ADT＋ENZ versus ADT alone was estimated as ￥7.18 million/QALY gained. ADT＋ABI and ADT＋APA were dominated options (extended dominance). Budget impact analysis showed that incorporation of ENZ had a net budget impact of ￥57.19 billion, an 8.4% increase, over these 5 years. This amounted to a budgetary impact of ￥16,000 per patient per month at year 5. However, the number of patients with disease progressed to metastatic castration-resistant prostate cancer (mCRPC) would be reduced from 79,000 (without ENZ) to 65,000 (with ENZ), resulting in a 17% cost reduction within the mCRPC phase. In conclusion, ADT＋ENZ would be a cost-effective option, at the willingness to pay threshold of ￥7.5 million/QALY gained. Introduction of ENZ in the mHSPC treatment would result in a marginal increase in the total budget. However, ENZ is also expected to provide clinical benefits in reducing the number of patients with disease that would otherwise progress to mCRPC during these 5 years, resulting in cost savings in this phase.

[Life and Money? Life or Money? -Health Economic Assessment and Value Assessment for Oncology Medications].

Health economics seek to provide the information which can contribute to the rational decision making, towards the appropriate allocation of scarce healthcare resources. Through the COVID-19 pandemic, everyone has recognized that healthcare resource would not be infinite and general public would no longer permit too excessive resource allocation for healthcare area, which might cause the conflict against other social activities. Even under the Universal Health Coverage, some restriction for coverage should be implemented, to maintain the public health care system. The health economic evaluation, or cost-effectiveness evaluation could be used for coverage decision of healthcare intervention for public health system, as it aimed to assess both costs and health outcome of candidate intervention against the conventional ones. The ICER, additional costs divided by additional outcomes could be used as"benchmark"of cost-effectiveness. The QALYs, quality-adjusted life years, was widely used as a"common"outcome measure, which enables us to evaluate interventions regardless of type of the diseases. However, cost-effectiveness data, or cost data with QALY data should not be the"only"benchmark value for decision making. Various aspects, outside of costs and QALYs, such as productivity losses and family spillovers, would constitute the"value"of interventions. How to evaluate the value of healthcare interventions must be differed from how to evaluate the cost-effectiveness of them.