論文 - 漆原　尚巳

Searching for potential surrogate endpoints of overall survival in clinical trials for patients with prostate cancer

Maeda H., Takeda K., Urushihara H., Kurokawa T.

Cancer Reports （Cancer Reports）  4 （ 3 ）  2021年06月

研究論文（学術雑誌）, 共著, 査読有り

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Background: The purpose of this study was to investigate the correlation between overall survival (OS) and other clinical outcomes in patients with prostate cancer. Further, we conducted subgroup analysis in the correlation of OS. Aim: This study intended to investigate potential surrogate endpoints of OS for prostate cancer by examining the correlation between OS and the other endpoints. Methods: We performed a systematic review through a literature search by computer-based searches of the Medline database (January 1965 and May 2014). Results: The contents of 115 studies with endpoint as OS were analyzed in our study. Our results showed that 47.8% (55/115) of the studies used progression-free survival as an endpoint besides OS, followed by time to progression (43.5% [50/115]) and PSA response (40.9% [47/115]). Also, the relationship between OS and each surrogate endpoint was examined using the hazard ratio (HR) by a Bayesian hybrid model for random effect multivariate meta-analysis. Our results showed that the endpoint that had the highest correlation with OS was progression-free survival (PFS) with an estimated marginal correlation of 0.939 (95%CI: 0.900, 0.967). Furthermore, our stratified analysis identified PFS in castration-resistant prostate cancer patients (0.937), in sensitive patients (0.932), in none of chemotherapy patients (0.929), in first line of the chemotherapy (0.948), in patients who received no Docetaxel previously (0.942), in both symptomatic and asymptomatic patients (0.950), in patients who received only chemotherapy (0.956), and in phase III (0.960), time to progression (TTP) in castration-resistant prostate cancer (CRPC) patients (0.942), in metastasis patients (0.948), in both symptomatic and asymptomatic patients (0.953), in patients who received only chemotherapy (0.938), and in Phase III (0.927) as endpoints, which showed a lower limit for 95% CI of estimated marginal correlation ≥0.850 with overall survival. Conclusions: Our study suggests that PFS is a potential surrogate endpoint of OS in clinical trials for patients with prostate cancer. It also suggests potential surrogate endpoints for CRPC and locally advanced prostate cancer.

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Study factors associated with the incompletion of clinical trials that include pediatric patients: a retrospective analysis of the European Clinical Trials Database and a lesson from the European region

Tanemura N, Sasaki T, Sato J, Urushihara H.

Trials 2021年03月

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電子診療録由来の診療情報データベースを用いたコントロール不良の小児喘息患者を対象としたモンテルカストと吸入ステロイド薬の有効性比較可能性の検討

高橋 透(慶応義塾大学 院薬), 漆原 尚巳

日本薬学会年会要旨集(0918-9823)141年会    27 2021年03月

研究論文（学術雑誌）, 責任著者

大規模病院情報データベースを用いた認知症患者における抗精神病薬の使用実態調査

佐藤 應気(慶応義塾大学 薬), 漆原 尚巳

日本薬学会年会要旨集(0918-9823)141年会    27 2021年03月

研究論文（学術雑誌）, 責任著者

Behavioral changes and hygiene practices of older adults in Japan during the first wave of COVID-19 emergency

Arai Y, Oguma Y, Abe Y, Takayama M, Hara A, Urushihara H, Takebayashi T.

BMC Geriatr 2021年02月

研究論文（学術雑誌）

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Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with anticonvulsants in a Japanese population: Matched case-control and cohort studies

Fukasawa T, Takahashi H, Takahashi K, Tanemura N, Amagai M, Urushihara H.

Allergol Int    335 - 342 2021年02月

研究論文（学術雑誌）, 共著

Searching for potential surrogate endpoints of overall survival in clinical trials for patients with prostate cancer

Maeda H, Takeda K, Urushihara H, Kurokawa T.

Cancer Rep (Hoboken) 2021年01月

研究論文（学術雑誌）

Regulatory Science Meets Epidemiology.

漆原 尚巳

薬剤疫学 （一般社団法人 日本薬剤疫学会）  26 （ Supplement ） S47 - S47 2021年

最終著者, 責任著者,  ISSN  13420445

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医療情報データベースを用いるための Outcome Definition Repository（ODR）の構築 ―日本薬剤疫学会 ODR-Task Force 報告―

井上 慧哉, 岩上 将夫, 小野 利展, 北島 行雄, 木村 友美, 佐藤 泉美, 杉田 玲夢, 杉山 大典, 原 梓, 宮崎 真, 米倉 寛, 漆原 尚巳

薬剤疫学 （一般社団法人 日本薬剤疫学会）  26 （ Supplement ） S158 - S159 2021年

最終著者, 責任著者,  ISSN  13420445

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欧米の動向を踏まえた、日本における抗てんかん薬の開発を目的とした小児臨床試験の有効性評価項目に関する実態調査

小坂 麻里子(慶応義塾大学 薬学部医薬品開発規制科学講座), 漆原 尚巳, 種村 菜奈枝

臨床薬理(0388-1601) 51   S366 2020年10月

研究論文（学術雑誌）, 責任著者

The first survey of gap between the actual labelling and efficacy information of functional substances in food under the regulatory processes in Japan

Tanemura N., Machii Y., Urushihara H.

Journal of Functional Foods （Journal of Functional Foods）  72 2020年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  17564646

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© 2020 The Author(s) To make well-informed choices, consumers need access to reliable and clear messages regarding the benefits of functional substances in food. This study identified foods with function claims (FFCs) in Japan that had a gap between actual labeling and efficacy information of functional substances not visible on their food package. Between April 1, 2015, to July 20, 2018, 1,310 FFCs were submitted to the regulatory agency and analyzed. The proportion of FFCs with a gap was highest in the health claim category of blood pressure management (79.5%), followed by neutral fat reduction in blood (75%) and suppression of blood sugar spikes (73.4%). These gaps are attributable to differences in food development strategy. Thus, to ensure the quality of benefit communication on FFC to consumers, scientific evidence regarding health claims of functional substances should be managed in an integrated manner.

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Real World Survey of Patient Engagement Status in Clinical Research: The First Input from Japan

Tanemura N., Sasaki T., Sato J., Urushihara H.

Patient （Patient）  13 （ 5 ） 623 - 632 2020年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1178-1661

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Background: The updated international draft guidelines, the “General Considerations for Clinical Studies, ICH E8 (R1)”, state that patient engagement ensures that all perspectives are captured in the research process; however, this is not well understood, specifically in Japan. Objective: This study examined the current status and perceptions of patient engagement in clinical research from the perspectives of patient groups, pharmaceutical corporations, and researchers in Japan, using anonymous self-administered questionnaires. Methods: Three online surveys were conducted with patient groups (n = 100), pharmaceutical corporations (n = 66), and researchers (n = 300) in May and June 2019. The main variables were the current status and the current perception of patient engagement in clinical research. Results: The response rate was 71% for patient groups and 85% for pharmaceutical corporations, and there were 300 valid responses (emergence rate: 4.9%) from researchers. Experiences with clinical research involving patient engagement were reported by 76.5% of the patients, 21.4% of the pharmaceutical corporations, and 51.7% of the researchers. Patient groups reported three major factors that negatively impacted their relationship with pharmaceutical corporations and researchers: (1) ‘lack of understanding of the benefits of partnering’; (2) ‘lack of transparency or openness’; and (3) ‘unclear or ill-defined processes’. Conclusions: Pharmaceutical corporations in Japan have less experience with patient engagement in clinical research than other stakeholders. A neutral connecting system among the stakeholders with a constructive co-learning system will allow effective involvement/engagement of patient groups for enhancing the effectiveness of clinical research.

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自発報告に基づくシグナル検出ができること，できないこと ―その理論と実践―

漆原尚巳

医薬品情報学 21 （ 4 ） 135 - 141 2020年

研究論文（学術雑誌）, 単著, 筆頭著者, 最終著者, 責任著者, 査読有り

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Survey on off-label use of antineoplastic agents in pediatric patients using a large-scale medical database in japan

Kuroda M., Nakamura A., Tanemura N., Nakakuni M., Sato J., Urushihara H.

Japanese Journal of Clinical Pharmacology and Therapeutics （Japanese Journal of Clinical Pharmacology and Therapeutics）  51 （ 6 ） 307 - 316 2020年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  03881601

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A number of drugs without pediatric indication are used off-label in infants and children who are described as "therapeutic orphans". This practice is widespread and constitutes a global issue. We conducted a drug utilization study using a large-scale electronic medical record(EMR)database to explore off-label prescription of anticancer drugs in pediatric patients. The EMR database was provided by Medical Data Vision(MDV). The subjects of the present study were pediatric patients aged from 0 to 14 years who were prescribed anticancer drugs and enrolled in the database between January 2016 and December 2017. We surveyed the number of patients who were prescribed these drugs outside the approved age window. Of 700 pediatric patients included in this study, 277 patients(40％) were prescribed anticancer drugs off-label; especially, 182 patients were prescribed"cytotoxic antibiotics and related substances"according to the WHO ATC classification, predominantly pirarubicin(140 patients). Since pirarubicin has not been approved in overseas countries, it is difficult to apply for pediatric indication utilizing the development promotion schemes such as the"public knowledge-based application(kouchi-shinsei)", and other drug development schemes have to be considered. Only a few subjects(0 to 3％)were prescribed anticancer drugs with pediatric indication but outside the approved age range. The prescribed doses［median(min-max)］of methotrexate and cytarabine were 15(2.8-21200)mg and 60(3-9000)mg, respectively. The dose ranges of these drugs were wide compared to the other drugs in the study. It was speculated that these high doses were probably used as high-dose therapy according to clinical guidelines, within the framework of clinical research. Considering that anticancer drugs generally have narrow safety margins, drug development for approval of pediatric indication should be promoted to provide safe and effective treatments for pediatric patients.

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大規模病院情報データベースを用いた小児患者における抗悪性腫瘍薬の適応外使用に関する実態調査

2. 黒田万由子, 中村彩夏, 種村菜奈枝, 中國正祥, 佐藤淳子, 漆原尚巳

臨床薬理 51 （ 6 ） 307 - 316 2020年

共著, 責任著者

機械学習を用いた医薬品の潜在的リスクの予測

西川 景太(慶応義塾大学), 種村 菜奈枝, 矢向 高弘, 漆原 尚巳

医療情報学連合大会論文集(1347-8508)39回     512 - 513 2019年11月

研究論文（学術雑誌）, 責任著者

Influenza vaccination effectiveness for people aged under 65 years in Japan, 2013/2014 season: Application of a doubly robust method to a large-scale, real-world dataset

Shibata N., Kimura S., Hoshino T., Urushihara H.

BMC Infectious Diseases （BMC Infectious Diseases）  19 （ 1 ） 586 2019年07月

研究論文（学術雑誌）, 共著, 最終著者, 責任著者, 査読有り

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© 2019 The Author(s). Background: Influenza vaccination is recognized as a primary public health intervention which prevents the illness of patients and relieves the societal burdens of influenza for medical community as well as the economy. To date, no effectiveness study of influenza vaccination has been conducted including a large population with a wide age span, in Japan. Here, we evaluated the clinical effectiveness of influenza vaccination in a large Japanese population. Methods: We conducted a cohort study using a large-scale claims database for employee health care insurance plans. Vaccination status was identified using plan records for influenza vaccination subsidies. We excluded people aged 65 years or more because of the unavailability of vaccination records. Effectiveness of vaccination in preventing influenza and its complication was evaluated with doubly robust methods using inversed probability treatment weighting to adjust health conscious behaviours and other confounders. Results: During the 2013/2014 influenza season, 369,425 subjects with age range from 1 to 64 years were eligible. Vaccination rate was 39.5% and an estimated odds ratio (OR) for influenza onset was 0.775 after doubly robust adjustment. Age-stratified ORs were significantly reduced in all age groups; lowest in subjects aged 1 to 4 years (0.600) and highest in those aged 13 to 19 (0.938). ORs for all the influenza complication outcomes were also statistically significant (0.403-0.709). Conclusions: We confirmed the clinical effectiveness of influenza vaccination in people aged 1 to 64 years. Influenza vaccination significantly prevented influenza onset and was more effective in reducing secondary risks of influenza complications.

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悪性腫瘍に関する医師主導臨床試験の結果公表状況調査

八田朋大, 三宅真二, 山川直利, 漆原尚巳

レギュラトリーサイエンス学会誌 2019年

薬学部におけるレギュラトリーサイエンスの基礎となる医薬品開発教育の実態調査

崔允瑄, 三宅真二, 種村菜奈枝, 漆原尚巳

レギュラトリーサイエンス学会誌 9 （ 3 ）  2019年

Utility of a specific health checkup database containing lifestyle behaviors and lifestyle diseases for employee health insurance in Japan

Fukasawa T., Tanemura N., Kimura S., Urushihara H.

Journal of Epidemiology （Journal of Epidemiology）  30 （ 2 ） 57 - 66 2019年

共著, 最終著者, 責任著者, 査読有り,  ISSN  09175040

　概要を見る

© 2019 Toshiki Fukasawa et al. T. Background: The Japanese Ministry of Health, Labour and Welfare introduced Specific Health Checkups (SHC) to identify individuals at risk of metabolic syndrome (MS). This study aimed to describe the SHC database developed by the Japan Medical Data Center Co., Ltd. (JMDC) as a means of exploring lifestyle behaviors and lifestyle diseases among working generations. Methods: We conducted a retrospective, cross-sectional study of employees and their families using the JMDC-SHC database to describe the prevalence of lifestyle behaviors (smoking, exercise, dietary habits, drinking habits, and sleeping) and lifestyle diseases (MS, hypertension, dyslipidemia, and diabetes mellitus). Results were compared with data from the 2015 National Health and Nutrition Survey (NHNS) in Japan as a benchmark. Results: All 646,869 enrollees in the JMDC-SHC database were included, of whom 66.5% were men. Age ranged from 40–74 years. Compared with the results of the NHNS, the JMDC-SHC subjects were younger and had fewer MS components and a lower prevalence of diabetes and hypertension. Subjects in their 40s were most likely to have unhealthy lifestyle behaviors in all age groups (eg, smoking: 41.0% in men and 10.2% in women). The SHC group had more favorable behaviors overall, but underweight was more prevalent in the SHC females. Conclusions: The JMDC-SHC population showed different lifestyle and lifestyle disease profiles to the NHNS population, probably due to its different age, gender, and employment distributions. Development of healthcare policies and plans for working generations would benefit from the selection of an age-and employment-appropriate database.

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