OBJECTIVE：The purpose of this study was to examine the problems of tracking patients by single facility for diseases that may be provided by specialists and in collaboration with regional healthcare providers during drug treatment and the applicability of an administrative claims database in Japan as a possible solution to these problems. METHODS：This retrospective cohort study utilized data from the DeSC database (from June 2018 to August 2022). First, we reported the number of facilities visited by patients with chronic thromboembolic pulmonary hypertension (CTEPH) on drug therapy, the frequency of visits at each facility, and new prescriptions of pulmonary vasodilators to identify possible transfers and concurrent consultations during drug therapy. We then reported the number of new diseases with possible adverse events at the facility where antithrombotic prescriptions were initiated and at other facilities among CTEPH patients who visited multiple facilities. RESULTS：We extracted 106 patients of CTEPH patients that were prescribed anticoagulants (77 patients in the multi-facility group and 29 patients in the single-facility group). The mean frequency of visits was 10.1 months/year (standard deviation 2.5) in the single-facility group and 10.4 months/year (standard deviation 2.1) in the multi-facility group, respectively. Whereas, the frequency of visits to only the facility that antithrombotic prescriptions were initiated in the multi-facility group was about half, at 6.5 months/year (standard deviation 4.0). For pulmonary vasodilators, out of the 18 patients (19 events) in the multi-facility group who had the initiation of prescription for pulmonary vasodilators at a facility other than where antithrombotic prescriptions were initiated, 13 of the patients (14 events) did not have the same prescription confirmed at the facility where antithrombotic prescriptions were initiated. These results indicate that CTEPH is a reasonable disease for patients to visit multiple facilities during drug treatment. In the multi-facility group, the newly diagnosed diseases confirmed at facilities other than the one where antithrombotic prescriptions were initiated and not confirmed at the facility where the antithrombotic prescriptions were initiated were：18/19 events of bleeding, 0/1 event of interstitial pulmonary diseases, 17/19 events of upper gastrointestinal motility disorders, 1/1 event of thyroid dysfunction, and 0/0 event of retinal disorders. CONCLUSION：This study showed that there may be safety information that cannot be picked up solely by the facility where the drug prescription was initiated due to multiple facility visits associated with diverse treatments. In cases where specialists may collaborate with community health care providers to treat a target disease during drug treatment, the generation of safety information through a patient-traceable an administrative claims database should be considered for the implementation of appropriate pharmacovigilance activities.

OBJECTIVE：The purpose of this study was to examine the problems of tracking patients by single facility for diseases that may be provided by specialists and in collaboration with regional healthcare providers during drug treatment and the applicability of an administrative claims database in Japan as a possible solution to these problems. METHODS：This retrospective cohort study utilized data from the DeSC database (from June 2018 to August 2022). First, we reported the number of facilities visited by patients with chronic thromboembolic pulmonary hypertension (CTEPH) on drug therapy, the frequency of visits at each facility, and new prescriptions of pulmonary vasodilators to identify possible transfers and concurrent consultations during drug therapy. We then reported the number of new diseases with possible adverse events at the facility where antithrombotic prescriptions were initiated and at other facilities among CTEPH patients who visited multiple facilities. RESULTS：We extracted 106 patients of CTEPH patients that were prescribed anticoagulants (77 patients in the multi-facility group and 29 patients in the single-facility group). The mean frequency of visits was 10.1 months/year (standard deviation 2.5) in the single-facility group and 10.4 months/year (standard deviation 2.1) in the multi-facility group, respectively. Whereas, the frequency of visits to only the facility that antithrombotic prescriptions were initiated in the multi-facility group was about half, at 6.5 months/year (standard deviation 4.0). For pulmonary vasodilators, out of the 18 patients (19 events) in the multi-facility group who had the initiation of prescription for pulmonary vasodilators at a facility other than where antithrombotic prescriptions were initiated, 13 of the patients (14 events) did not have the same prescription confirmed at the facility where antithrombotic prescriptions were initiated. These results indicate that CTEPH is a reasonable disease for patients to visit multiple facilities during drug treatment. In the multi-facility group, the newly diagnosed diseases confirmed at facilities other than the one where antithrombotic prescriptions were initiated and not confirmed at the facility where the antithrombotic prescriptions were initiated were：18/19 events of bleeding, 0/1 event of interstitial pulmonary diseases, 17/19 events of upper gastrointestinal motility disorders, 1/1 event of thyroid dysfunction, and 0/0 event of retinal disorders. CONCLUSION：This study showed that there may be safety information that cannot be picked up solely by the facility where the drug prescription was initiated due to multiple facility visits associated with diverse treatments. In cases where specialists may collaborate with community health care providers to treat a target disease during drug treatment, the generation of safety information through a patient-traceable an administrative claims database should be considered for the implementation of appropriate pharmacovigilance activities.

Objective：To show that it is possible to capture pregnant women by identifying newborns and their mothers using JMDC database and examine a generalizability to Japan.Methods：We identified a newborn who was born between 2016 and 2020 and his/her mother using health insurance association's registry owned by JMDC Inc. First, we identified a newborn whose relationship to the insured was “child” and who joined the health insurance association at birth month. And we linked a woman member aged 18 to 49 who belongs to the same family at the newborn's birth month to the newborn as a mother. We assessed a generalizability of these mothers and newborns obtained from this method by an age distribution of mother at birth month and proportion of newborn against women aged between 18 and 49 using Vital Statistics, National Census, and Population Estimates in Japan as index.Results：We identified 194,036 mother-newborn pairs in JMDC database from 2016 to 2020. The mean mother's age at newborn's birth was 31.9. On the other hand, the number of births in Japan during the same period was 4,538,786, and the mean mothers' age was 31.5. Number of newborns per 1,000 women in JMDC database in 2020 was 19.0, and that in Japan was 37.0.Conclusion：We concluded that our method of identifying pregnant women and newborns is useful for study of pregnant women and newborns.

Objective：To show that it is possible to capture pregnant women by identifying newborns and their mothers using JMDC database and examine a generalizability to Japan.Methods：We identified a newborn who was born between 2016 and 2020 and his/her mother using health insurance association's registry owned by JMDC Inc. First, we identified a newborn whose relationship to the insured was “child” and who joined the health insurance association at birth month. And we linked a woman member aged 18 to 49 who belongs to the same family at the newborn's birth month to the newborn as a mother. We assessed a generalizability of these mothers and newborns obtained from this method by an age distribution of mother at birth month and proportion of newborn against women aged between 18 and 49 using Vital Statistics, National Census, and Population Estimates in Japan as index.Results：We identified 194,036 mother-newborn pairs in JMDC database from 2016 to 2020. The mean mother's age at newborn's birth was 31.9. On the other hand, the number of births in Japan during the same period was 4,538,786, and the mean mothers' age was 31.5. Number of newborns per 1,000 women in JMDC database in 2020 was 19.0, and that in Japan was 37.0.Conclusion：We concluded that our method of identifying pregnant women and newborns is useful for study of pregnant women and newborns.

Objective：To investigate the purposes, reasons, and issues of Real World Data (RWD) utilization by data source among pharmaceutical companies in Japan. In this study, we focus on RWDs such as Electronic Medical Records (EMR), Personal Health Records, and registries, which are expected to be utilized in the future. Design：Web based-questionnaire surveyMethods：This questionnaire survey was conducted on 68 companies affiliated with Clinical Evaluation Expert Committee in Japan Pharmaceutical Manufacturers Association from January 18th to February 14th in 2022. In principle, the survey covered four divisions (Clinical development, Pharmacovigilance, Medical Affairs, Health Economics & Outcomes Research) of each company, and other cross-functional divisions were also acceptable to answer. Results：［Background］ Of 40 companies out of 68 companies, 102 respondents were responded to this survey. Overall, 75 respondents (73.5％) have “experienced in utilization of RWD”, and 12 (11.8％) have “experienced in considering utilization of RWD”. ［Utilization by RWD Type］ By data source, hospital-based claim data was the most frequently used (65 cases, 63.7％), followed by insurance-based claim data (61 cases, 59.8％), surveys (38 cases, 37.3％), and EMR (36 cases, 35.3％) in experienced RWD utilization. Conclusion：This study revealed the current status and issues related to the utilization of each type of RWDs in Japan. It is expected that data linkage among multiple RWDs and data standardization enable further utilization of RWDs in future.

Objective：To investigate the purposes, reasons, and issues of Real World Data (RWD) utilization by data source among pharmaceutical companies in Japan. In this study, we focus on RWDs such as Electronic Medical Records (EMR), Personal Health Records, and registries, which are expected to be utilized in the future. Design：Web based-questionnaire surveyMethods：This questionnaire survey was conducted on 68 companies affiliated with Clinical Evaluation Expert Committee in Japan Pharmaceutical Manufacturers Association from January 18th to February 14th in 2022. In principle, the survey covered four divisions (Clinical development, Pharmacovigilance, Medical Affairs, Health Economics & Outcomes Research) of each company, and other cross-functional divisions were also acceptable to answer. Results：［Background］ Of 40 companies out of 68 companies, 102 respondents were responded to this survey. Overall, 75 respondents (73.5％) have “experienced in utilization of RWD”, and 12 (11.8％) have “experienced in considering utilization of RWD”. ［Utilization by RWD Type］ By data source, hospital-based claim data was the most frequently used (65 cases, 63.7％), followed by insurance-based claim data (61 cases, 59.8％), surveys (38 cases, 37.3％), and EMR (36 cases, 35.3％) in experienced RWD utilization. Conclusion：This study revealed the current status and issues related to the utilization of each type of RWDs in Japan. It is expected that data linkage among multiple RWDs and data standardization enable further utilization of RWDs in future.

Objective: To evaluate the real-world risk of hypocalcemia in Japanese patients with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) newly initiated on denosumab (PRALIA®) versus those receiving DMARDs alone.Design: Observational cohort study utilizing data obtained from the Medical Information Database Network (MID-­NET®) in Japan.Methods: Patients were eligible if they had a prescription record for any DMARD during the study period (July 2016–­December 2020), with their RA diagnosis ＜30 days before the date of DMARD prescription. Primary and secondary outcomes included the incidence of hypocalcemia (serum calcium level ＜8.50 mg/dL), and severe hypocalcemia (serum calcium level ＜7.00 mg/dL), respectively. Data was classified according to denosumab-exposure versus non-exposure, with outcomes assessed during the follow-up period. Results: Overall, 4,222 patients (denosumab-exposed patients: N＝293; non-exposed patients: N＝3,929) met the study criteria. Hypocalcemia occurred in 4.8％（95％CI: 2.6-­7.9) of denosumab-exposed patients and 1.0％（95％CI: 0.7-­1.4) of non-exposed patients, for an adjusted risk ratio (RR) of 1.67（95％CI: 0.90-­3.10).Conclusion: The incidence of hypocalcemia was increased in denosumab-exposed patients compared with non-exposed patients with RA in this observational study utilizing data from MID-­NET®. As the adjusted RR of hypocalcemia with denosumab was modest, current risk management strategies outlined in the package insert are appropriate.

This document reports the results of a questionnaire survey conducted among pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association as part of a collaborative research project within the AMED Research on Regulatory Science of Pharmaceuticals and Medical Devices ‘Research for the promotion of the utilization of real-world evidence in the pharmaceutical regulatory system and the harmonization of international regulations, and for the proposal of an ideal system in Japan’ (Principal Investigator： Harumasa Nakamura, National Center of Neurology and Psychiatry). This survey is the first domestic attempt to clarify the current state of development and utilization of data for companion applications (CPs) in pharmaceuticals. It is expected that the widespread development and use of pharmaceutical CPs will enhance the collection of patient-reported outcomes (PROs), which in turn will foster the utilization of real-world data (RWD) under pharmaceutical regulations. In anticipation that the results of this survey will contribute to this promotion, we are publishing the entire questionnaire results in this report.

Objective: To evaluate the real-world risk of hypocalcemia in Japanese patients with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) newly initiated on denosumab (PRALIA®) versus those receiving DMARDs alone.Design: Observational cohort study utilizing data obtained from the Medical Information Database Network (MID-NET®) in Japan.Methods: Patients were eligible if they had a prescription record for any DMARD during the study period (July 2016-December 2020), with their RA diagnosis ＜30 days before the date of DMARD prescription. Primary and secondary outcomes included the incidence of hypocalcemia (serum calcium level ＜8.50 mg/dL), and severe hypocalcemia (serum calcium level ＜7.00 mg/dL), respectively. Data was classified according to denosumab-exposure versus non-exposure, with outcomes assessed during the follow-up period. Results: Overall, 4,222 patients (denosumab-exposed patients: N＝293; non-exposed patients: N＝3,929) met the study criteria. Hypocalcemia occurred in 4.8％（95％CI: 2.6-­7.9) of denosumab-exposed patients and 1.0％（95％CI: 0.7-­1.4) of non-exposed patients, for an adjusted risk ratio (RR) of 1.67（95％CI: 0.90-­3.10).Conclusion: The incidence of hypocalcemia was increased in denosumab-exposed patients compared with non-exposed patients with RA in this observational study utilizing data from MID-­NET®. As the adjusted RR of hypocalcemia with denosumab was modest, current risk management strategies outlined in the package insert are appropriate.