論文 - 漆原　尚巳

Comparison of Regulations and Status of Promoting Drug Development and Authorization of Pediatric Indications among Japan, the United States and the United Kingdom

Suwa M., Miyake S., Urushihara H.

Japanese Journal of Clinical Pharmacology and Therapeutics （Japanese Journal of Clinical Pharmacology and Therapeutics）  53 （ 6 ） 225 - 234 2022年

最終著者, 責任著者,  ISSN  03881601

　概要を見る

Pediatric drug development is challenging due to various difficulties in clinical evaluation and inadequate economic return over development cost. The legislative measures have been taken in several countries, including the European Union（EU）and the United States（US）, to advance drug development in pediatrics because of its importance in disease management. We compared legislation related to promotion of pediatric drug development in the US, the United Kingdom（UK）and Japan. Next, we set the US, a pioneer in addressing off-label use in children, as the standard against which to compare the approval status of pediatric indications in Japan and the UK. According to the drug labels, we identified 72 products approved for pediatric indications in the US between January 2016 and April 2020 which were also approved for adults or children in both Japan and the UK. We calculated the percentage of products with pediatric indications and analyzed the development status of products without pediatric indications. In the UK, 83％（60/72）of products had pediatric indications. Of the 12 products without pediatric indications, four were investigated in clinical trials or planned to be developed for pediatric use. In contrast, the percentage of products with pediatric indications in Japan was 44％（32/72）, and of the 40 products without pediatric indications, only two were in development for pediatric use. All of the products reviewed by the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs of the Japanese Ministry of Health, Labour and Welfare were indicated for pediatric patients. In contrast, only about half（9/19）of the drugs with orphan drug designation had pediatric indications. With reference to the regulatory frameworks in the US and UK, the＂Designation of Pharmaceuticals for Specific Use＂, established in the 2019 revision of the Pharmaceuticals and Medical Devices Law（PMDL）, may offer the better means to promote pediatric drug development in Japan.

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Comparison of the incidence of bleeding between baloxavir marboxil and other anti-influenza drugs among outpatients with influenza virus infection: A retrospective cohort study using an employment-based health insurance claims

Hara A, Hara K, Komeda T, Ogura E, Miyazawa S, Kobayashi C, Fujiwara M, Yoshida M, Urushihara H.

（Pharmacoepidemiol Drug Saf）  2021年12月

研究論文（学術雑誌）

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Comparison of the incidence of bleeding between baloxavir marboxil and other anti-influenza drugs among outpatients with influenza virus infection: A retrospective cohort study using an employment-based health insurance claims database in Japan

Hara A., Hara K., Komeda T., Ogura E., Miyazawa S., Kobayashi C., Fujiwara M., Yoshida M., Urushihara H.

Pharmacoepidemiology and Drug Safety （Pharmacoepidemiology and Drug Safety）  31 （ 6 ） 623 - 631 2021年12月

研究論文（学術雑誌）, 共著, 最終著者, 査読有り,  ISSN  1099-1557

　概要を見る

Purpose: Alerts for bleeding events are included in the Japanese package inserts of some anti-influenza drugs, including baloxavir marboxil and oseltamivir. However, there are few reports on the incidence of bleeding events during treatment with anti-influenza drugs. This large-scale quantitative assessment compared the incidence of bleeding events in influenza patients treated with baloxavir and other anti-influenza drugs and in untreated patients. Methods: This retrospective cohort study used a large-scale Japanese employment-based health insurance claims database provided by JMDC Inc. and included outpatients diagnosed with influenza between October 1, 2018 and April 11, 2019. Bleeding events were identified by International Classification of Diseases 10th revision codes. Incidences were compared between patients treated with baloxavir or neuraminidase inhibitors and untreated patients. Odds ratios were calculated after exact matching to adjust for potential confounders. Results: Among 529 201 influenza episodes, 30 964 were untreated and 498 237 were treated with anti-influenza drugs: baloxavir, 207 630; oseltamivir, 143 722; zanamivir, 28 208; peramivir, 5304; laninamivir, 113 373. Crude incidence proportions for total bleeding up to 20 days after influenza diagnosis were similar among treated groups, with a slightly higher value for peramivir (0.21% vs. 0.19% for baloxavir, oseltamivir, zanamivir, and laninamivir), and 0.30% in untreated patients. After exact matching, the incidence of bleeding for baloxavir was similar to that for other anti-influenza treatments (odds ratios for baloxavir were 0.90–0.99 compared to other therapies). Conclusions: Based on real-world observation using a large-scale claims database, a similar incidence of bleeding events was observed in recipients of the different anti-influenza drugs.

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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 Geriatrics （BMC Geriatrics）  21 （ 1 ）  2021年12月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Background: On April 7, 2020, Japan declared a state of emergency due to the first wave of coronavirus disease 2019 (COVID-19) with the associated social distancing likely to have had a great impact on older adults’ lifestyle and health. This study aimed to explore the behavioral changes and personal hygiene practices in relation with background psychosocial and health characteristics of older adults during the COVID-19 emergency. Methods: A cross-sectional telephonic survey was conducted with the participants of the Kawasaki Aging and Wellbeing Project (KAWP), an on-going longitudinal cohort study of older adults aged 85 or older. The interviews were conducted using a structured questionnaire consisting of 11 closed questions regarding behavioral changes and personal hygiene practices during the state of emergency. Sociodemographic and health data were obtained from the KAWP baseline survey conducted 2.2 years before the telephonic survey. Results: Overall, 487 participants from the KAWP responded to the telephonic survey (response rate: 89.2%). 94.5% of the respondents reported no changes in basic lifestyle habits, such as eating, sleeping, smoking, and drinking, whereas 28.1% reported a decrease in physical activity, and 54.6% reported going out less frequently. One-third of the respondents reported a decrease in the number of people to converse with, as well as the amount of time to converse. For personal hygiene practices, 93.8% reported wearing a mask when they went out, and 50.3% reported an increased frequency of handwashing. Multiple logistic regression analysis revealed that engagement in physical activity at baseline (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.23–3.08), smartphone ownership (OR = 2.15, 95% CI = 1.33–3.47), and visual impairment (OR = 1.79; 95% CI = 1.10–2.91) were independently associated with decreased physical activity during the COVID-19 emergency. Female respondents and smartphone ownership were significantly associated with more frequent handwashing. Conclusions: The study revealed that older adults in an urban setting responded to the COVID-19 emergency with behavioral changes. The findings of this study have implications for the design of preventive strategies to maintain the health and wellbeing of at-risk older adults.

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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 （Trials）  22 （ 1 ）  2021年12月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Background: Incomplete clinical trials for pediatric drug development result in a lack of adequate scientific evidence for providing appropriate medication to pediatric populations; this is especially true for Japan. Thus, using the European Clinical Trials Database (EudraCT), this study aimed to identify the factors related to the study design and administration that lead to incompletion of clinical trials that included pediatric patients. Methods: We focused on clinical trials that included patients under the age of 18 registered in the database, named as the European Clinical Trials Database between January 1, 2014, and December 31, 2018. Two groups of trials were identified: “all cases completed” and “not all cases completed,” reflecting whether they were completed in all participating countries/regions or not. To identify the factors of the occurrence of “not all cases completed,” a logistic regression analysis was performed to calculate the odds ratios and 95% confidence intervals. In total, 142 clinical trials (95 “all cases completed” and 47 “not all cases completed”) were analyzed. Results: The logistic regression analysis showed the number of countries in which a clinical trial was conducted to be the only significant factor (odds ratio: 1.3; 95% confidence interval: 1.1-1.5); this was identified as the primary factor for the occurrence of “not all cases completed” in the clinical trials that included pediatric patients. Conclusion: Our findings suggest that the feasibility of clinical trials that include pediatric patients, such as whether the countries in which the trial is to be conducted are suitable, must be considered prior to the trial.

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Lifestyle behaviors associated with the initiation of renal replacement therapy in Japanese patients with chronic kidney disease: a retrospective cohort study using a claims database linked with specific health checkup results

Hara A., Hirata T., Okamura T., Kimura S., Urushihara H.

Environmental Health and Preventive Medicine （Environmental Health and Preventive Medicine）  26 （ 1 ） 102 - 102 2021年12月

研究論文（学術雑誌）, 共著, 最終著者, 責任著者, 査読有り,  ISSN  1342078X

　概要を見る

Background: Chronic kidney disease (CKD) is an independent risk factor for progression to an end-stage renal disease requiring dialysis or kidney transplantation. We investigated the association of lifestyle behaviors with the initiation of renal replacement therapy (RRT) among CKD patients using an employment-based health insurance claims database linked with specific health checkup (SHC) data. Methods: This retrospective cohort study included 149,620 CKD patients aged 40–74 years who underwent a SHC between April 2008 and March 2016. CKD patients were identified using ICD-10 diagnostic codes and SHC results. We investigated lifestyle behaviors recorded at SHC. Initiation of RRT was defined by medical procedure claims. Lifestyle behaviors related to the initiation of RRT were identified using a Cox proportional hazards regression model with recency-weighted cumulative exposure as a time-dependent covariate. Results: During 384,042 patient-years of follow-up by the end of March 2016, 295 dialysis and no kidney transplantation cases were identified. Current smoking (hazard ratio: 1.87, 95% confidence interval, 1.04─3.36), skipping breakfast (4.80, 1.98─11.62), and taking sufficient rest along with sleep (2.09, 1.14─3.85) were associated with the initiation of RRT. Conclusions: Among CKD patients, the lifestyle behaviors of smoking, skipping breakfast, and sufficient rest along with sleep were independently associated with the initiation of RRT. Our study strengthens the importance of monitoring lifestyle behaviors to delay the progression of mild CKD to RRT in the Japanese working generation. A substantial portion of subjects had missing data for eGFR and drinking frequency, warranting verification of these results in prospective studies.

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日本・米国・英国における小児用医薬品の開発推進策と承認状況調査

諏訪 美月(慶応義塾大学 薬学部医薬品開発規制科学講座), 三宅 真二, 漆原 尚巳

日本臨床薬理学会学術総会抄録集(2436-5580)42回    1 2021年12月

責任著者

日本と欧州における希少疾病用医薬品の指定取り消し理由と開発の実態調査

野口 千鶴(慶応義塾大学 薬学部医薬品開発規制科学講座), 三宅 真二, 漆原 尚巳

日本臨床薬理学会学術総会抄録集(2436-5580)42回    2 2021年12月

責任著者

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ODR-Task Force報告

井上 慧哉(慶応義塾大学 大学院薬学研究科), 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(1342-0445) 26   S158 - S159 2021年11月

研究論文（学術雑誌）, 責任著者

医療情報データベースを用いた日本の抗菌薬による感染症治療の実態調査

雨宮 優理(慶応義塾大学 薬学部医薬品開発規制科学講座), 原 梓, 田中 啓太, 漆原 尚巳

薬剤疫学(1342-0445) 26   S106 - S107 2021年11月

研究論文（学術雑誌）, 責任著者

有害事象予測に向けたElectronic Hospital Recordsに対する分散表現の適用

石川 智貴(慶応義塾大学 大学院理工学研究科総合デザイン工学専攻), 矢向 高弘, 漆原 尚巳

薬剤疫学(1342-0445) 26   S119 - S120 2021年11月

研究論文（学術雑誌）

抗菌薬・抗真菌薬の使用とスティーヴンス・ジョンソン症候群及び中毒性表皮壊死症のリスク

深澤 俊貴(京都大学 大学院医学研究科社会健康医学系専攻薬剤疫学分野デジタルヘルス学講座), 漆原 尚巳, 高橋 勇人, 川上 浩司

薬剤疫学(1342-0445) 26   S131 - S132 2021年11月

研究論文（学術雑誌）

三本の矢(マッチング、自己対照、トレンド分析)によるバロキサビルマルボキシルの出血リスク評価

米田 卓司(塩野義製薬 データサイエンス部), 原 梓, 原 華苗, 小倉 江里子, 藤原 正和, 宮澤 昇吾, 吉田 真奈美, 漆原 尚巳

薬剤疫学(1342-0445) 26   S137 - S138 2021年11月

研究論文（学術雑誌）, 責任著者

診療報酬請求データベースを用いた新型コロナウイルス感染症患者の重症化予測モデルの構築、及び重症化因子の探索

八重樫 昇吾(慶応義塾大学 大学院薬学研究科), 漆原 尚巳, 宮澤 孝慈, 市原 泰介, 山田 雄矢, 星野 崇宏

薬剤疫学(1342-0445) 26   S140 - S141 2021年11月

研究論文（学術雑誌）, 責任著者

慶応義塾大学薬学部におけるCOVID-19ワクチン職域接種サーベイランス(中間報告)

奥村 佳穂(慶応義塾大学 薬学部医薬品開発規制科学講座), 原 梓, 杉山 大典, 星野 崇宏, 矢向 高弘, 横山 裕一, 漆原 尚巳

薬剤疫学(1342-0445) 26   S143 - S144 2021年11月

研究論文（学術雑誌）, 責任著者

本邦における前立腺肥大症治療薬のアドヒアランス調査

前川 拓也(慶応義塾大学 大学院薬学研究科医薬品開発規制科学講座), 原 梓, 漆原 尚巳

薬剤疫学(1342-0445) 26   S145 - S146 2021年11月

研究論文（学術雑誌）, 責任著者

使用成績調査の代替としてのRWDを用いた医薬品の有用性評価に関する研究

川上 峻弥(慶応義塾大学 大学院薬学研究科医薬品開発規制科学講座), 星野 崇宏, 原 梓, 漆原 尚巳

薬剤疫学(1342-0445) 26   S154 - S155 2021年11月

研究論文（学術雑誌）, 責任著者

Believability of real-world evidence (RWE) for informed regulatory decisions

Leclerc Jacinthe, Brodovicz Kimberly G., Chang Stephen, Assimon Magdalene M., Urushihara Hisashi, Girman Cynthia J.

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 30   3 - 3 2021年08月

最終著者, 責任著者,  ISSN  1053-8569

Comparison of the incidence of bleeding between anti-influenza drugs among outpatients for the influenza virus infection: A retrospective study using an employment-based health insurance claims database in Japan

Hara Azusa, Hara Kanae, Komeda Takuji, Ogura Eriko, Miyazawa Shogo, Kobayashi Chiduru, Fujiwara Masakazu, Yoshida Manami, Urushihara Hisashi

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 30   182 - 183 2021年08月

最終著者, 責任著者,  ISSN  1053-8569

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.

Allergology International （Allergology International）  70 （ 3 ） 335 - 342 2021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,  ISSN  13238930

　概要を見る

Background: Evidence for the risk and incidence of anticonvulsant-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Japan is scarce. Methods: We conducted a matched case–control study using a large-scale Japanese claims database. SJS/TEN cases were identified using a claims-based algorithm developed in a previous study (sensitivity 76.9%, specificity 99.0%). Conditional logistic regression with Firth's bias correction to address an issue of rare events was used to estimate odds ratios (ORs) for SJS/TEN for each anticonvulsant use (90 days before the index date) versus non-use. 90-day cumulative incidence of SJS/TEN per 100,000 new users was calculated for 33 anticonvulsants. Causality between anticonvulsant use and SJS/TEN in each exposed case was assessed using the algorithm of drug causality for epidermal necrolysis (ALDEN) score. Results: From 5,114,492 subjects, we selected 71 SJS/TEN cases and 284 controls. We observed significantly increased ORs for SJS/TEN among new users of carbamazepine (OR 68.00) and lamotrigine (OR 36.00) with ALDEN scores of “probable” or higher. Cumulative incidence of SJS/TEN was 93.83 for carbamazepine and 84.33 for lamotrigine. One case newly exposed to phenytoin which developed SJS/TEN was rated “unlikely” in ALDEN causality, resulting in cumulative incidence of 66.27. Cumulative incidence of SJS/TEN was 25.23 for levetiracetam, 7.52 for clonazepam, and 1.23 for diazepam, but their ALDEN scores were “very unlikely”. Conclusions: This study is the first to document the differential risk of SJS/TEN for anticonvulsants in a real-world setting in Japan. Exposure to carbamazepine and lamotrigine was associated with an increased risk of SJS/TEN.

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