ナレッジデータベースを活用したバイオマーカーの初期臨床開発ステージへの導入
「はじめに」日米欧州医薬品規制調和国際会議(ICH)E16ガイドライン(2011年)の冒頭で「バイオマーカーを利用することは, より安全で有効な医薬品又はバイオテクノロジー応用医薬品の利用可能性を促進し, 用量選択に指針を与え, それら医薬品のリスク・ベネフィット特性を改善できる可能性がある」と述べられており, 1) 概念的にバイオマーカーは研究段階から新薬承認申請用試験・市販後試験まで必要な用途に応じ活用可能である. 欧米メガファーマでは, 腫瘍治療分野における分子標的薬の薬剤応答性患者層別化を目的とするコンパニオン診断バイオマーカー検証を含む後期臨床試験, あるいは心循環器治療分野における...
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| Published in | YAKUGAKU ZASSHI Vol. 134; no. 4; pp. 473 - 483 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | Japanese |
| Published |
公益社団法人 日本薬学会
01.04.2014
日本薬学会 |
| Online Access | Get full text |
| ISSN | 0031-6903 1347-5231 |
| DOI | 10.1248/yakushi.13-00248-3 |
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| Abstract | 「はじめに」日米欧州医薬品規制調和国際会議(ICH)E16ガイドライン(2011年)の冒頭で「バイオマーカーを利用することは, より安全で有効な医薬品又はバイオテクノロジー応用医薬品の利用可能性を促進し, 用量選択に指針を与え, それら医薬品のリスク・ベネフィット特性を改善できる可能性がある」と述べられており, 1) 概念的にバイオマーカーは研究段階から新薬承認申請用試験・市販後試験まで必要な用途に応じ活用可能である. 欧米メガファーマでは, 腫瘍治療分野における分子標的薬の薬剤応答性患者層別化を目的とするコンパニオン診断バイオマーカー検証を含む後期臨床試験, あるいは心循環器治療分野における市販後アウトカム(死亡率等)を予想するバイオマーカーをエンドポイントとした後期臨床試験等(2008-2009年)がそれぞれ49件あるいは29件実施されたと報告されている. 2) 一方, 初期臨床開発ステージでは開発可能な適応症の選択や, 医薬品としての最大ポテンシャルを引き出すための薬剤による作動性範囲を見極めるために開発品プロファイルを追及することも重要である. |
|---|---|
| AbstractList | 「はじめに」日米欧州医薬品規制調和国際会議(ICH)E16ガイドライン(2011年)の冒頭で「バイオマーカーを利用することは, より安全で有効な医薬品又はバイオテクノロジー応用医薬品の利用可能性を促進し, 用量選択に指針を与え, それら医薬品のリスク・ベネフィット特性を改善できる可能性がある」と述べられており, 1) 概念的にバイオマーカーは研究段階から新薬承認申請用試験・市販後試験まで必要な用途に応じ活用可能である. 欧米メガファーマでは, 腫瘍治療分野における分子標的薬の薬剤応答性患者層別化を目的とするコンパニオン診断バイオマーカー検証を含む後期臨床試験, あるいは心循環器治療分野における市販後アウトカム(死亡率等)を予想するバイオマーカーをエンドポイントとした後期臨床試験等(2008-2009年)がそれぞれ49件あるいは29件実施されたと報告されている. 2) 一方, 初期臨床開発ステージでは開発可能な適応症の選択や, 医薬品としての最大ポテンシャルを引き出すための薬剤による作動性範囲を見極めるために開発品プロファイルを追及することも重要である. |
| Author | 後藤, 信治 鈴木, 將之 |
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| DOI | 10.1248/yakushi.13-00248-3 |
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| References | 9) Goto N., Saijo T., Kuwahara Y., Farumashia, 48, 643-647 (2012). 24) European Medicines Agency (EMA), Guideline on Bioanalytical Method Validation, 2011. 6) European Medicines Agency (EMA), Guideline on Clinical Investigation of Medicinal Products in the Treatment of Hypertension, 2010. 1) Ministry of Health, Labour and Welfare, Pharmaceutical and Food Safety Bureau, PFSB/ELD Notification No. 0120-1, ICH E16: Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure and Format of Qualification Submissions, 20 January, 2011. 17) European Medicines Agency (EMA), European public assessment reports: 〈http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d124〉, cited 10 September, 2013. 10) European Medicines Agency (EMA), Clinical Investigation of Medicinal Products in the Treatment of Chronic Obstructive Pulmonary Disease (COPD), 2012. 18) European Medicines Agency (EMA), Clinical Investigation of Medicinal Products indicated for the Treatment of Psoriasis, 2004. 19) Krueger J. G., Fretzin S., Suárez-Fariñas M., Haslett P. A., Phipps K. M., Cameron G. S., McColm J., Katcherian A., Cueto I., White T., Banerjee S., Hoffman R. W., J. Allergy Clin. Immunol., 130, 145-154 (2012). 29) U.S. Food and Drug Administration (FDA), Medical Devices, Device Advice, Medical De vice Databases: 〈http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Databases/default.htm〉, cited 10 September, 2013. 2) Merchant M., “Biomarkers in Late Stage Clinical Trials Applications, Opportunities and Activities of Leading Players,” Business Insights, Menlo Park, 2010. 5) Timmerman P., Herling C., Stoellner D., Jaitner B., Pihl S., Elsby K., Henderson N., Barroso B., Fischmann S., Companjen A., Versteilen A., Bates S., Kingsley C., Kunz U., Bioanalysis, 4, 1883-1894 (2012). 15) Pharmaceuticals and Medical Devices Agency (PMDA): 〈http://www.info.pmda.go.jp/info/iyaku_index.html〉, cited 10 September, 2013. 28) National Cancer Institute (NCI), FactSheet, Interpreting Laboratory Test Results, reviewed January, 2003: 〈http://www.cancer.gov/cancertopics/factsheet/detection/laboratorytests〉, cited 10 September, 2013. 30) Clinical and Laboratory Standards Institute (CLSI), CLSI Standards Center: 〈http://www.clsi.org/standards/〉, cited 10 September, 2013. 21) Suárez-Fariñas M., Fuentes-Duculan J., Lowes M. A., Krueger J. G., J. Invest. Dermatol., 131, 391-400 (2011). 26) Hougton R., Gouty D., Allinson J., Green R., Losauro M., Lowes S., LeLacheur R., Garofolo F., Couerbe P., Bronner S., Struwe P., Schiebl C., Sangster T., Pattison C., Islam R., Garofolo W., Pawula M., Buonarati M., Hayes R., Cameron M., Nicholson R., Harman J., Wieling J., Boer T. D., Reuschel S., Cojocaru L., Harter T., Malone M., Nowatzke W., Bioanalysis, 4, 2439-2446 (2012). 8) European Medicines Agency (EMA), Guideline on Clinical Investigation of Medicinal Products for the Treatment of Multiple Sclerosis, 2006. 11) European Medicines Agency (EMA), Clinical Investigation of Medicinal Products for the Treatment of Attention-deficit/Hyperactivity Disorder, 2010. 25) Yoneyama T., Inoue N., Tachiki H., Togashi K., Nakayama A., Kudo T., Shimizi H., Katori N., Pharmaceutical and Medical Device Regulatory Science, 143, 750-760 (2012). 31) Japanese Committee for Clinical Laboratory Standards, “An approved Guideline for the Quality Management of Specimens for Molecular Methods: The Procurement, Transport, and Preparation of Specimens, JCCLS MM5A1,” Gakuzyutsu-Koukoku-sha, Tokyo, 2011. 3) Toriyama Y., OPIR Views and Actions, 28, 1-6 (2009). 22) Wong M., Ziring D., Korin Y., Desai S., Kim S., Lin J., Gjertson D., Braun J., Reed E., Singh R. R., Clin. Immunol., 126, 121-136 (2008). 14) Japan Council for Quality Health Care, EBM Medical Information Division, Medical Information Network Distribution Service (Minds): 〈http://minds.jcqhc.or.jp/n/medical_user_main.php?main_tab=1&menu_id=9〉, cited 10 September, 2013. 7) European Medicines Agency (EMA), Guideline on the Evaluation of Medicinal Products for Cardiovascular Disease Prevention, 2010. 13) Toho University Media Center, Guideline Database: 〈http://www.mnc.toho-u.ac.jp/mmc/guideline/〉, cited 10 September, 2013. 23) U.S. Depertment of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine, “Guidance for Industry, Bioanalytical Method Validation,” 2001. 20) Johnson-Huang L. M., Pensabene C. A., Shah K. R., Pierson K. C., Kikuchi T., Lentini T., Gilleaudeau P., Sullivan-Whalen M., Cueto I., Khatcherian A., Hyder L. A., Suárez-Fariñas M., Krueger J. G., Lowes M. A., PLoS One, 7, e30308 (2012). 16) U.S. Food and Drug Administration (FDA), Drug information, Drugs@FDA: 〈http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm〉, cited 10 September, 2013. 12) MedlinePlus, Health Topics, A service of the U.S. National Library of Medicine, National Institutes of Health (NIH): 〈http://www.nlm.nih.gov/medlineplus/〉, cited 10 September, 2013. 27) Lee J. W., Devanarayan V., Barrett Y. C., Weiner R., Allinson J., Fountain S., Keller S., Weinryb I., Green M., Duan L., Rogers J. A., Millham R., O'Brien P. J., Sailstad J., Khan M., Ray C., Wagner J. A., Pharm. Res., 23, 312-328 (2006). 4) Biomarkers Definitions Working Group: Atkinson A. J., Colburn W. A., DeGruttola V. G., DeMets D. L., Downing G. J., Hoth D. F., Oates J. A., Peck C. C., Schooley R. T., Spilker B. A., Woodcock J., Zeger S. L., Clin. Pharmacol. Ther., 69, 89-95 (2001). |
| References_xml | – reference: 17) European Medicines Agency (EMA), European public assessment reports: 〈http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d124〉, cited 10 September, 2013. – reference: 3) Toriyama Y., OPIR Views and Actions, 28, 1-6 (2009). – reference: 18) European Medicines Agency (EMA), Clinical Investigation of Medicinal Products indicated for the Treatment of Psoriasis, 2004. – reference: 27) Lee J. W., Devanarayan V., Barrett Y. C., Weiner R., Allinson J., Fountain S., Keller S., Weinryb I., Green M., Duan L., Rogers J. A., Millham R., O'Brien P. J., Sailstad J., Khan M., Ray C., Wagner J. A., Pharm. Res., 23, 312-328 (2006). – reference: 24) European Medicines Agency (EMA), Guideline on Bioanalytical Method Validation, 2011. – reference: 22) Wong M., Ziring D., Korin Y., Desai S., Kim S., Lin J., Gjertson D., Braun J., Reed E., Singh R. R., Clin. Immunol., 126, 121-136 (2008). – reference: 31) Japanese Committee for Clinical Laboratory Standards, “An approved Guideline for the Quality Management of Specimens for Molecular Methods: The Procurement, Transport, and Preparation of Specimens, JCCLS MM5A1,” Gakuzyutsu-Koukoku-sha, Tokyo, 2011. – reference: 7) European Medicines Agency (EMA), Guideline on the Evaluation of Medicinal Products for Cardiovascular Disease Prevention, 2010. – reference: 13) Toho University Media Center, Guideline Database: 〈http://www.mnc.toho-u.ac.jp/mmc/guideline/〉, cited 10 September, 2013. – reference: 16) U.S. Food and Drug Administration (FDA), Drug information, Drugs@FDA: 〈http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm〉, cited 10 September, 2013. – reference: 25) Yoneyama T., Inoue N., Tachiki H., Togashi K., Nakayama A., Kudo T., Shimizi H., Katori N., Pharmaceutical and Medical Device Regulatory Science, 143, 750-760 (2012). – reference: 1) Ministry of Health, Labour and Welfare, Pharmaceutical and Food Safety Bureau, PFSB/ELD Notification No. 0120-1, ICH E16: Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure and Format of Qualification Submissions, 20 January, 2011. – reference: 8) European Medicines Agency (EMA), Guideline on Clinical Investigation of Medicinal Products for the Treatment of Multiple Sclerosis, 2006. – reference: 5) Timmerman P., Herling C., Stoellner D., Jaitner B., Pihl S., Elsby K., Henderson N., Barroso B., Fischmann S., Companjen A., Versteilen A., Bates S., Kingsley C., Kunz U., Bioanalysis, 4, 1883-1894 (2012). – reference: 14) Japan Council for Quality Health Care, EBM Medical Information Division, Medical Information Network Distribution Service (Minds): 〈http://minds.jcqhc.or.jp/n/medical_user_main.php?main_tab=1&menu_id=9〉, cited 10 September, 2013. – reference: 19) Krueger J. G., Fretzin S., Suárez-Fariñas M., Haslett P. A., Phipps K. M., Cameron G. S., McColm J., Katcherian A., Cueto I., White T., Banerjee S., Hoffman R. W., J. Allergy Clin. Immunol., 130, 145-154 (2012). – reference: 21) Suárez-Fariñas M., Fuentes-Duculan J., Lowes M. A., Krueger J. G., J. Invest. Dermatol., 131, 391-400 (2011). – reference: 2) Merchant M., “Biomarkers in Late Stage Clinical Trials Applications, Opportunities and Activities of Leading Players,” Business Insights, Menlo Park, 2010. – reference: 4) Biomarkers Definitions Working Group: Atkinson A. J., Colburn W. A., DeGruttola V. G., DeMets D. L., Downing G. J., Hoth D. F., Oates J. A., Peck C. C., Schooley R. T., Spilker B. A., Woodcock J., Zeger S. L., Clin. Pharmacol. Ther., 69, 89-95 (2001). – reference: 26) Hougton R., Gouty D., Allinson J., Green R., Losauro M., Lowes S., LeLacheur R., Garofolo F., Couerbe P., Bronner S., Struwe P., Schiebl C., Sangster T., Pattison C., Islam R., Garofolo W., Pawula M., Buonarati M., Hayes R., Cameron M., Nicholson R., Harman J., Wieling J., Boer T. D., Reuschel S., Cojocaru L., Harter T., Malone M., Nowatzke W., Bioanalysis, 4, 2439-2446 (2012). – reference: 28) National Cancer Institute (NCI), FactSheet, Interpreting Laboratory Test Results, reviewed January, 2003: 〈http://www.cancer.gov/cancertopics/factsheet/detection/laboratorytests〉, cited 10 September, 2013. – reference: 29) U.S. Food and Drug Administration (FDA), Medical Devices, Device Advice, Medical De vice Databases: 〈http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Databases/default.htm〉, cited 10 September, 2013. – reference: 10) European Medicines Agency (EMA), Clinical Investigation of Medicinal Products in the Treatment of Chronic Obstructive Pulmonary Disease (COPD), 2012. – reference: 6) European Medicines Agency (EMA), Guideline on Clinical Investigation of Medicinal Products in the Treatment of Hypertension, 2010. – reference: 9) Goto N., Saijo T., Kuwahara Y., Farumashia, 48, 643-647 (2012). – reference: 11) European Medicines Agency (EMA), Clinical Investigation of Medicinal Products for the Treatment of Attention-deficit/Hyperactivity Disorder, 2010. – reference: 30) Clinical and Laboratory Standards Institute (CLSI), CLSI Standards Center: 〈http://www.clsi.org/standards/〉, cited 10 September, 2013. – reference: 15) Pharmaceuticals and Medical Devices Agency (PMDA): 〈http://www.info.pmda.go.jp/info/iyaku_index.html〉, cited 10 September, 2013. – reference: 20) Johnson-Huang L. M., Pensabene C. A., Shah K. R., Pierson K. C., Kikuchi T., Lentini T., Gilleaudeau P., Sullivan-Whalen M., Cueto I., Khatcherian A., Hyder L. A., Suárez-Fariñas M., Krueger J. G., Lowes M. A., PLoS One, 7, e30308 (2012). – reference: 12) MedlinePlus, Health Topics, A service of the U.S. National Library of Medicine, National Institutes of Health (NIH): 〈http://www.nlm.nih.gov/medlineplus/〉, cited 10 September, 2013. – reference: 23) U.S. Depertment of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine, “Guidance for Industry, Bioanalytical Method Validation,” 2001. |
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| Title | ナレッジデータベースを活用したバイオマーカーの初期臨床開発ステージへの導入 |
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