Development of a Model for Quantitative Assessment of Newborn Screening in Japan Using the Analytic Hierarchy Process.

Whether or not conditions should be included in publicly funded newborn screening (NBS) programs should be discussed according to objective and transparent criteria. Certain criteria have been developed for the introduction of NBS programs in the context of individual countries; however, there are no standard selection criteria for NBS programs in Japan. This study aimed to develop a quantitative scoring model to assess newborn screening that incorporates the views of a variety of stakeholders in Japan. The five recommended eligibility criteria for NBS were stratified based on previous studies and expert opinions, using the analytic hierarchy process. We conducted a cross-sectional, web-based questionnaire targeting a wide range of people involved in NBS to investigate pairwise comparisons of the evaluation items between February and April of 2022. There were 143 respondents. Most of our respondents (44.1%) were physicians. Fifty-eight respondents (40.6%) had been engaged in NBS-related research or work for more than 10 years. The distribution of allocation points was the highest for 'intervention', 'screening test', 'follow-up setting', 'economic evaluation', and 'disease/condition', in that order. The algorithm in this study will guide decision makers in collecting and evaluating objective data, thus enabling transparent discussions to occur.

Regional disparity in the provision of rehabilitation services using the open data from the Japanese national claims database: an ecological study.

OBJECTIVES: There are few reports on regional differences in the supply/utilisation balance and provision of rehabilitation services. This study analysed those regional differences in Japan to help policymakers provide more uniform and efficient rehabilitation services and optimally allocate related resources. DESIGN: An ecological study. SETTING: 47 prefectures and 9 regions in Japan in 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measures were 'supply/utilisation (S/U) ratio', calculated by dividing rehabilitation supply converted to service units, by rehabilitation utilisation and 'utilisation/expected utilisation (U/EU) ratio', calculated by dividing utilisation by EU. The EU was defined as utilisation expected from the demography in each area. Data required to calculate these indicators were collected from open sources such as the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan. RESULTS: The S/U ratios were higher in Shikoku, Kyusyu, Tohoku and Hokuriku regions, and lower in Kanto and Tokai regions. The number of rehabilitation providers per population was higher mostly in the western part of Japan and lower mostly in the eastern part. The U/EU ratios were also higher mostly in the western part, and lower mostly in the eastern part such as Tohoku and Hokuriku regions. The same trend was seen for cerebrovascular disease and musculoskeletal disorder rehabilitation, which accounted for approximately 84% of rehabilitation services. For disuse syndrome rehabilitation, such a trend did not exist, and the U/EU ratio differed by prefectures. CONCLUSIONS: The large surplus in rehabilitation supply in the western part was attributed to the greater number of providers, while the smaller surplus in Kanto and Tokai regions was due to the smaller amount of supply. The number of rehabilitation services used was lesser in the eastern part such as Tohoku and Hokuriku regions, indicating regional differences in the provision of rehabilitation services.

Impacts of the preceding cancer-specific health-related quality of life instruments on the responses to the subsequent EQ-5D-5L.

BACKGROUND: In clinical studies, the EQ-5D-5L is often employed with disease-specific health-related quality of life instruments. The questions in the former are more general than the latter; however, it is known that responses to general questions can be influenced by preceding specific questions. Thus, the responses to the EQ-5D-5L have the possibility of being influenced by the preceding disease-specific health-related quality of life instruments. This may lead to bias in the cost-effectiveness analysis results. Therefore, this study aimed to evaluate the impact of the preceding cancer-specific health-related quality of life instruments on the EQ-5D-5L responses. METHODS: We prepared questionnaire booklets containing the EQ-5D-5L, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Functional Assessment of Cancer Therapy General with different orders. Using a quasi-randomized design, they were distributed to the patients undergoing drug therapy for advanced cancer, who were classified into three groups: Groups 1, 2, and 3 (the EQ-5D-5L placed first, second, and last, respectively). We compared the EQ-5D-5L index and the missingness of EQ-5D-5L among the groups. RESULTS: The mean EQ-5D-5L index was 0.796, 0.760, and 0.789 for groups 1 (n = 300), 2 (n = 306), and 3 (n = 331), respectively. The difference between Groups 2 and 1 was - 0.036 (95% CI - 0.065 to - 0.007; p = 0.015). The proportion of patients with an incomplete EQ-5D-5L was 0.11, 0.11, and 0.05 for Groups 1, 2, and 3, respectively. The difference of the proportions between group 3 and 1 and between 3 and 2 was - 0.06 (95% CI - 0.10 to - 0.02; p = 0.003) and - 0.06 (95% CI - 0.10 to - 0.02; p = 0.003), respectively. CONCLUSIONS: Although the EQ-5D-5L index differed according to the instrument orders, the difference size would not be considerably larger than the minimally important difference. The patients tended to complete the EQ-5D-5L when they were placed at the end of the questionnaire.

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting. STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty. RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening. CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

Gradient Boosted Tree Approaches for Mapping European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Onto 5-Level Version of EQ-5D Index for Patients With Cancer.

OBJECTIVES: This study aimed to develop direct and response mapping algorithms from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 onto the 5-level version of EQ-5D index based on the gradient boosted tree (GBT), a promising modern machine learning method. METHODS: We used the Quality of Life Mapping Algorithm for Cancer study data (903 observations from 903 patients) for training GBTs and testing their predictive performance. In the Quality of Life Mapping Algorithm for Cancer study, patients with advanced solid tumor were enrolled, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and 5-level version of EQ-5D were simultaneously evaluated. The Japanese value set was used for direct mapping, whereas the Japanese and US value sets were used for response mapping. We trained the GBTs in the training data set (80%) with cross-validation and tested the predictive performance measured by the root mean squared error (RMSE), mean absolute error (MAE), and mean error in the test data set (20%). RESULTS: The RMSE and MAE in the test data set were larger in the GBT approaches than in the previously developed regression-based approaches. The mean error in the test data set tended to be smaller in the GBT approaches than in the previously developed regression-based approaches. CONCLUSIONS: The predictive performances in the RMSE and MAE did not improve by the GBT approaches compared with regression approaches. The flexibility of the GBT approaches had the potential to reduce overprediction and underprediction in poor and good health, respectively. Further research is needed to establish the role of machine learning methods in mapping a nonpreference-based measure onto health utility.

Identification of individuals benefiting from the kakaritsuke-yakuzaishi (family pharmacist) system in Japan: a retrospective cohort study using an employment-based health insurance claims database.

BACKGROUND: The kakaritsuke-yakuzaishi system (henceforth, the family pharmacist system) which provides more health services than those by general pharmaceutical practice, was implemented in Japan in April 2016. To distribute medical resources and medical care expenditures appropriately, identifying the possible major beneficiaries of this system is essential. By analyzing administrative claims data through this retrospective cohort study, we identified modifiers of the potential benefits of the system. Further, we integrated the identified modifiers into a scoring system that indicates the possible benefitting subpopulations. METHODS: We obtained data about individuals under 75 years old routinely using community pharmacies in Japan from the JMDC database. We classified the individuals as users or non-users. We used claims related to "choufukutouyaku-sougosayoutou-boushi-kasan (additional therapeutic duplication and drug interaction [TDDI] prevention fees)" filed between April 2018 and March 2020, which indicate that individuals' prescriptions were modified to adjust leftover drugs or to avoid TDDI as indicators of potential benefit. We estimated adjusted absolute risk differences and 95% confidence intervals for product terms using multiple generalized linear regression models. We included the factors whose 95% confidence interval lower limits did not reach 0 in the multiple logistic regression models for developing a scoring system. RESULTS: The eligible cohort included 162,340 individuals (1,214 users and 161,126 non-users). The leftover drugs adjustment significantly increased for individuals prescribed antidepressants. However, as only one modifier was identified, we did not develop a scoring system for the leftover drugs adjustment. For TDDI prevention, the following factors were included in the scoring system: being female, being prescribed ≥ 6 drug types, using ≥ 2 medical institutions, and being prescribed proton pump inhibitors, antibiotics, probiotics, or traditional Japanese herbal medicines. The developed scoring system for TDDI prevention scored "female" and "traditional Japanese herbal medicines prescription" factors higher than other factors. CONCLUSIONS: Individuals who are female or prescribed traditional Japanese herbal medicines, or antidepressants may benefit significantly from the family pharmacist system.

[Impact of Change in Community Pharmacists' Role on Their Estimated Demand].

Pharmacists play a key role in optimizing the safe and effective use of medicines in the super-aged society in Japan. Recently, community pharmacists' role has been transformed and expanded to provide patient-centered care. This study aimed to simulate a change in the demand for community pharmacists resulting from this shift in their role, from 2019 to 2035. The change in demand was estimated by the number of prescriptions obtained from publicly available sources of information. The number of required community pharmacists was calculated separately for full-time and part-time pharmacists and the pharmacists engaged in home medical care. This number was calculated using the estimated demand, the number of prescriptions dispensed per day, and annual working days. We evaluated the effect of changes in the working conditions, which include changes in the dispensing process time, rate of part-time staff and their work time, and number of home medical care per day, on the number of community pharmacists. When the number of prescriptions dispensed per day was set at 19.8, the demand for community pharmacists was estimated as 188,314 in 2035. Furthermore, due to the changes in the working conditions, the demand is expected to change from 153,362 to 266,944. Although the increasing provision of drug information time leads to an increasing number of pharmacists, combining it with work efficiency services could prevent or decrease it. The optimal supply and demand balance of community pharmacists should be determined by both, promoting pharmaceutical care services and improving work efficiency.

Direct health care cost of treatment and medication of biliary atresia patients using the National Database of Health Insurance Claims and Specific Health Checkups.

BACKGROUND: Treatment of biliary atresia (BA), which typically requires an initial surgical intervention called the Kasai procedure (KP) and possible liver transplant (LT) afterwards, is quite resource-intensive and would affect patients and families for a lifetime; yet a comprehensive view of the economic burden has not been reported. We estimated direct health care costs from the public payer perspective using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. METHODS: Children newly diagnosed at ages 0 days to 4 years between April 2010 and September 2019 were identified. Costs of treatment were estimated for six phases of care: prediagnosis, KP and inpatient hospitalization, follow-up after KP, pre-transplant checkup, LT and inpatient hospitalization, and follow-up after LT. RESULTS: Mean total prediagnosis medical cost was $6847 (USD) and KP and inpatient hospitalization was $42,157 per year. Follow-up after KP was $15,499, and pre-transplant checkup after KP was $36,015 per year. Mean cost for LT and inpatient hospitalization was $105,334, and follow-up after liver transplant was $25,459 per year. CONCLUSIONS: Treatment of BA requires extensive medical resource consumption. The use of the comprehensive national database allowed us to estimate the costs which will be useful for health service planning and cost-effectiveness analysis.

Randomized Controlled Trial of Paper-Based at a Hospital versus Continual Electronic Patient-Reported Outcomes at Home for Metastatic Cancer Patients: Does Electronic Measurement at Home Detect Patients' Health Status in Greater Detail?

PURPOSE: This study aimed to determine whether continual electronic patient-reported outcome (ePRO) measurements at home can capture the fluctuations in health-related quality of life (HRQOL) scores between visits. METHODS: We performed a randomized controlled trial to compare the scores obtained by standard practice (paper-based measurements in the hospital) to scores by continuous measurement of ePRO at home. Metastatic cancer patients were randomly assigned to either the paper-based (n = 50) or the ePRO group (n = 52). EQ-5D-5L and EORTC QLQ C-30 scores were obtained on 3 different chemotherapy days in the paper-based group. Meanwhile, scores were obtained on the chemotherapy day and on days 3, 7, 10, and 14 in the ePRO group during 2 cycles. The first hypothesis of our study was that both scores at the same time points would be equivalent despite different measurement frequency, place, or mode of measurement. The second hypothesis was that PRO score-adjusted time would be different between the groups. For equivalence, the endpoint was the mean EQ-5D-5L index value on the chemotherapy day before the outpatient treatment. Only if equivalence was shown, quality-adjusted life-days (QALDs) were considered using all the data. RESULTS: The adjusted mean difference in the EQ-5D-5L index was determined to be -0.013 (95% confidence interval [CI]: -0.049 to 0.022); the 95% CI did not exceed the equivalence margin. Similarly, the mean difference in global health status (2.28 [95% CI: -2.55 to 7.11]) also showed equivalence. However, the QALD by EQ-5D-5L was significantly lower in the ePRO group by 1.36 per 30 d (95% CI: -2.22 to -0.51; P = 0.0021). CONCLUSIONS: Continual measurements of the HRQOL at home by ePRO may yield more detailed profiles of the HRQOL.

Mapping EORTC QLQ-C30 and FACT-G onto EQ-5D-5L index for patients with cancer.

BACKGROUND: To develop direct and indirect (response) mapping algorithms from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy General (FACT-G) onto the EQ-5D-5L index. METHODS: We conducted the QOL-MAC study where EQ-5D-5L, EORTC QLQ-C30, and FACT-G were cross-sectionally evaluated in patients receiving drug treatment for solid tumors in Japan. We developed direct and indirect mapping algorithms using 7 regression methods. Direct mapping was based on the Japanese value set. We evaluated the predictive performances based on root mean squared error (RMSE), mean absolute error, and correlation between the observed and predicted EQ-5D-5L indexes. RESULTS: Based on data from 903 and 908 patients for EORTC QLQ-C30 and FACT-G, respectively, we recommend two-part beta regression for direct mapping and ordinal logistic regression for indirect mapping for both EORTC QLQ-C30 and FACT-G. Cross-validated RMSE were 0.101 in the two methods for EORTC QLQ-C30, whereas they were 0.121 in two-part beta regression and 0.120 in ordinal logistic regression for FACT-G. The mean EQ-5D-5L index and cumulative distribution function simulated from the recommended mapping algorithms generally matched with the observed ones except for very good health (both source measures) and poor health (only FACT-G). CONCLUSIONS: The developed mapping algorithms can be used to generate the EQ-5D-5L index from EORTC QLQ-C30 or FACT-G in cost-effectiveness analyses, whose predictive performance would be similar to or better than those of previous algorithms.

Cost-Minimization Analysis of Deep-Brain Stimulation Using National Database of Japanese Health Insurance Claims.

OBJECTIVES: A new rechargeable dual-channel deep brain stimulation (DBS) system has been introduced for the treatment of Parkinson's disease and other movement disorders. However, the clinical value of the device, which has a high cost, remains unclear. MATERIALS AND METHODS: We conducted a cost-minimization analysis using a national database of health insurance claims in Japan. DBS-related costs were compared between rechargeable and non-rechargeable devices and estimated across a 20-year period. RESULTS: Although the price of rechargeable DBS was higher than that of non-rechargeable DBS, we observed total cost-savings of 8.4 million yen across 20 years by considering costs related to implantation surgery, frequency of replacement, and risk of complications. CONCLUSIONS: In this study, real-world evidence indicated that rechargeable dual-channel DBS is a reasonable choice for saving total medical costs. Price revisions should consider cost-effectiveness findings for medical devices.

Economic burden of community-acquired pneumonia among elderly patients: a Japanese perspective.

BACKGROUND: This study aimed to estimate the economic burden of community-acquired pneumonia (CAP) among elderly patients in Japan. In addition, the study evaluated the relationship between total treatment cost and CAP risk factors. METHODS: An administrative database was searched for elderly patients (≥ 65 years old) who had pneumonia (ICD-10 code: J12-J18) and an antibiotic prescription between 1 June 2014 and 31 May 2015. The all-cause total healthcare costs of outpatient and inpatient CAP episodes were calculated. RESULTS: This study evaluated data from 29,619 patients with CAP who experienced 14,450 outpatient CAP episodes and/or 20,314 inpatient CAP episodes. The mean ages were 77.5 ± 8.0 years and 81.5 ± 8.2 years among the outpatient and inpatient groups, respectively. The median treatment costs were US$346 (interquartile range: $195-551) per outpatient episode and US$4851 (interquartile range: $3313-7669) per inpatient episode. More severe cases had increased treatment costs at the treating hospitals. Male sex, diabetes, chronic obstructive pulmonary disease, and liver dysfunction were associated with increased total treatment costs, while dementia, dialysis, and rheumatism were associated with high costs of treating a CAP episode. CONCLUSIONS: The economic burden of CAP might be decreased by reducing the number of hospitalizations for mild CAP and the incidence of severe CAP. Therefore, preventative care (e.g. oral hygiene or pneumococcus vaccination) is recommended for patients with related risk factors, such as male sex, older age, diabetes, chronic obstructive pulmonary disease, liver dysfunction, rheumatism, dementia, or dialysis.

Clinical Data Interchange Standards Consortium Standardization of Biobank Data: A Feasibility Study.

The National Center Biobank Network (NCBN), consisting of six national centers (NCs) for advanced and specialized medical care, was launched in Japan in 2012 to collect biological specimens and health-related data. The common data formats of the six NCs, however, are not widely known outside the NCs. Therefore, we investigated whether the data elements collected by the NCBN could be made to conform to the international standards of the Clinical Data Interchange Standards Consortium (CDISC). We attempted to map the NCBN data elements (202 items) onto the Study Data Tabulation Model (SDTM), a set of CDISC standards on the submission format of electronic clinical data approved by the Food and Drug Administration. The results showed that all 202 items of the NCBN data could be mapped onto the SDTM and fulfilled 50%-70% of the required items of each domain specified in the SDTM. We concluded that, while the standardization of biobank data according to the CDISC standards is possible, there is a need to consider whether additional items must be included in the NCBN and to have experts familiar with the CDISC standards review the standardization needs.